FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Goldfarb, I Dumont, O Henry, D Barth, W AF Goldfarb, Ilona Dumont, Olivia Henry, Dana Barth, William TI The impact of hysterotomy technique at primary cesarean section on subsequent uterine rupture SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [Goldfarb, Ilona; Dumont, Olivia; Barth, William] Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Obstet & Gynecol Dept, Boston, MA 02114 USA. [Henry, Dana] UCSF, Div Maternal Fetal Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S275 EP S275 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600559 ER PT J AU Goldfarb, I Little, S Riley, L AF Goldfarb, Ilona Little, Sarah Riley, Laura TI Uptake of the combined tetanus, diphtheria and pertussis (Tdap) vaccine during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [Goldfarb, Ilona; Riley, Laura] Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Obstet & Gynecol Dept, Boston, MA 02114 USA. [Little, Sarah] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S261 EP S262 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600531 ER PT J AU March, M Modest, AM Gupta, M Ralston, S Brown, F AF March, Melissa Modest, Anna Merport Gupta, Munish Ralston, Steven Brown, Florence TI Does a change in screening guidelines change the risk profile and outcomes of the gestational diabetes population? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 34th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2014 CL New Orleans, LA SP Soc Maternal Fetal Med C1 [March, Melissa; Modest, Anna Merport; Gupta, Munish; Ralston, Steven] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brown, Florence] Joslin Diabet Ctr, Diabet Pregnancy Program, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2014 VL 210 IS 1 SU S BP S183 EP S183 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298KK UT WOS:000330322600360 ER PT J AU Burris, HH Camargo, CA AF Burris, Heather H. Camargo, Carlos A., Jr. TI Vitamin D and Gestational Diabetes Mellitus SO CURRENT DIABETES REPORTS LA English DT Article DE Vitamin D; 25-hydroxyvitamin D; Pregnancy; Gestational diabetes mellitus; GDM; Gestational diabetes ID D DEFICIENCY; OUTCOMES; PREGNANCY; METAANALYSIS; RISK; INSUFFICIENCY; DETERMINANTS; ASSOCIATION; PREVALENCE; OBESITY AB Gestational diabetes mellitus (GDM) complicates 7 %-14 % of pregnancies in the United States. Vitamin D deficiency also is common in pregnancy. Emerging evidence suggests that Vitamin D administration can improve insulin sensitivity and glucose tolerance, but whether vitamin D supplementation can prevent GDM is unknown. Observational studies provide conflicting evidence as to whether low serum 25-hydroxyvitmain D (25(OH) D) levels are associated with GDM. Two recent systematic reviews concluded that vitamin D deficiency is associated with a higher risk of GDM. However, these reviews are limited by the observational and diverse nature of the included studies. Of greatest concern is the inability to understand how important confounding variables such as race/ethnicity and adiposity might affect the association. Randomized controlled trial data remain limited but are critical to understanding whether supplementation with vitamin D beyond what is contained in routine prenatal vitamins will prevent GDM or improve glucose tolerance for women with GDM. C1 [Burris, Heather H.] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. [Burris, Heather H.] Boston Childrens Hosp, Div Newborn Med, Boston, MA 02215 USA. [Burris, Heather H.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Channing Div Network Med, Dept Med,Brigham & Womens Hosp, Boston, MA 02215 USA. RP Burris, HH (reprint author), Beth Israel Deaconess Med Ctr, Dept Neonatol, 330 Brookline Ave,RO 318, Boston, MA 02215 USA. EM heburris@bidmc.harvard.edu OI Burris, Heather/0000-0003-4510-9547 FU Klarman Family Foundation Scholars Program at Beth Israel Deaconess Medical Center; NIH/NIEHS [K23 ES022242] FX Dr. Burris's work is supported by the Klarman Family Foundation Scholars Program at Beth Israel Deaconess Medical Center and by NIH/NIEHS K23 ES022242. NR 37 TC 12 Z9 15 U1 1 U2 10 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD JAN PY 2014 VL 14 IS 1 AR 451 DI 10.1007/s11892-013-0451-3 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 288TQ UT WOS:000329635200003 PM 24277676 ER PT J AU Ba, D Babadi, B Purdon, PL Brown, EN AF Ba, Demba Babadi, Behtash Purdon, Patrick L. Brown, Emery N. TI Convergence and Stability of Iteratively Re-weighted Least Squares Algorithms SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE Compressive sampling; constrained maximum likelihood estimation; Gaussian scale mixtures; expectation-maximization algorithms; mathematical programming ID EM ALGORITHM; STABLE RECOVERY; SPARSE; MINIMIZATION; SIGNALS AB In this paper, we study the theoretical properties of iteratively re-weighted least squares (IRLS) algorithms and their utility in sparse signal recovery in the presence of noise. We demonstrate a one-to-one correspondence between the IRLS algorithms and a class of Expectation-Maximization (EM) algorithms for constrained maximum likelihood estimation under a Gaussian scale mixture (GSM) distribution. The EM formalism, as well as the connection to GSMs, allow us to establish that the IRLS algorithms minimize smooth versions of the l(nu) 'norms', for 0 < nu <= 1. We leverage EM theory to show that the limit points of the sequence of IRLS iterates are stationary points of the smooth "norm" minimization problem on the constraint set. We employ techniques from Compressive Sampling (CS) theory to show that the IRLS algorithm is stable, if the limit point of the iterates coincides with the global minimizer. We further characterize the convergence rate of the IRLS algorithm, which implies global linear convergence for nu = 1 and local super-linear convergence for 0 < nu < 1. We demonstrate our results via simulation experiments. The simplicity of IRLS, along with the theoretical guarantees provided in this contribution, make a compelling case for its adoption as a standard tool for sparse signal recovery. C1 [Ba, Demba; Babadi, Behtash; Purdon, Patrick L.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ba, Demba; Babadi, Behtash; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ba, D (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM demba@neurostat.mit.edu; behtash@nmr.mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu; enb@neurostat.mit.edu FU National Institutes of Health (NIH) [DP2-OD006454, R01-EB006385] FX This work was partially supported by National Institutes of Health (NIH) New Innovator Award DP2-OD006454 (to P. L. Purdon) and R01-EB006385 (to E.N. Brown and P.L. Purdon). NR 33 TC 13 Z9 15 U1 2 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-587X EI 1941-0476 J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD JAN PY 2014 VL 62 IS 1 BP 183 EP 195 DI 10.1109/TSP.2013.2287685 PG 13 WC Engineering, Electrical & Electronic SC Engineering GA 297YM UT WOS:000330291000015 ER PT J AU Duplan, MB Zalli, D Stephens, S Zenger, S Neff, L Oelkers, JM Lai, FPL Horne, W Rottner, K Baron, R AF Duplan, Martin Biosse Zalli, Detina Stephens, Sebastien Zenger, Serhan Neff, Lynn Oelkers, J. Margit Lai, Frank P. L. Horne, William Rottner, Klemens Baron, Roland TI Microtubule Dynamic Instability Controls Podosome Patterning in Osteoclasts through EB1, Cortactin, and Src SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX DEGRADATION; END-BINDING-PROTEINS; ACTIN RING FORMATION; BONE-RESORPTION; SEALING-ZONE; IN-VIVO; KINASE-ACTIVITY; PLUS-END; C-SRC; TYROSINE PHOSPHORYLATION AB In osteoclasts (OCs) podosomes are organized in a belt, a feature critical for bone resorption. Although microtubules (MTs) promote the formation and stability of the belt, the MT and/or podosome molecules that mediate the interaction of the two systems are not identified. Because the growing "plus" ends of MTs point toward the podosome belt, plus-end tracking proteins (+ TIPs) might regulate podosome patterning. Among the + TIPs, EB1 increased as OCs matured and was enriched in the podosome belt, and EB1-positive MTs targeted podosomes. Suppression of MT dynamic instability, displacement of EB1 from MT ends, or EB1 depletion resulted in the loss of the podosome belt. We identified cortactin as an Src-dependent interacting partner of EB1. Cortactin- deficient OCs presented a defective MT targeting to, and patterning of, podosomes and reduced bone resorption. Suppression of MT dynamic instability or EB1 depletion increased cortactin phosphorylation, decreasing its acetylation and affecting its interaction with EB1. Thus, dynamic MTs and podosomes interact to control bone resorption. C1 [Duplan, Martin Biosse; Zalli, Detina; Stephens, Sebastien; Zenger, Serhan; Neff, Lynn; Horne, William; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Oelkers, J. Margit; Lai, Frank P. L.; Rottner, Klemens] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Oelkers, J. Margit; Rottner, Klemens] Univ Bonn, Inst Genet, Bonn, Germany. [Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA USA. RP Baron, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM Roland_Baron@hms.harvard.edu OI Rottner, Klemens/0000-0003-4244-4198 FU NIH, NIAMS [AR054450, AR062054]; Deutsche Forschungsgemeinschaft [RO2414/1-2]; Fondation Bettencourt-Schueller; Fondation pour la Recherche Medicale FX This work was supported by grants from the NIH, NIAMS (AR054450 and AR062054 to R. B.), and the Deutsche Forschungsgemeinschaft (RO2414/1-2 to K. R.) and fellowships from the Fondation Bettencourt-Schueller and the Fondation pour la Recherche Medicale (to M. B. D.). NR 95 TC 13 Z9 13 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2014 VL 34 IS 1 BP 16 EP 29 DI 10.1128/MCB.00578-13 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 302DK UT WOS:000330581600002 ER PT J AU Pinho, MC Polaskova, P Kalpathy-Cramer, J Jennings, D Emblem, KE Jain, RK Rosen, BR Wen, PY Sorensen, AG Batchelor, TT Gerstner, ER AF Pinho, Marco C. Polaskova, Pavlina Kalpathy-Cramer, Jayashree Jennings, Dominique Emblem, Kyrre E. Jain, Rakesh K. Rosen, Bruce R. Wen, Patrick Y. Sorensen, A. Gregory Batchelor, Tracy T. Gerstner, Elizabeth R. TI Low Incidence of Pseudoprogression by Imaging in Newly Diagnosed Glioblastoma Patients Treated With Cediranib in Combination With Chemoradiation SO ONCOLOGIST LA English DT Article DE Pseudoprogression; Vascular endothelial growth factor; Cediranib; Glioblastoma ID BEVACIZUMAB PLUS IRINOTECAN; STANDARD RADIATION-THERAPY; TYROSINE KINASE INHIBITOR; MALIGNANT GLIOMA PATIENTS; HIGH-GRADE GLIOMA; RECURRENT GLIOBLASTOMA; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE; BLOOD PERFUSION; PHASE-3 TRIAL AB Background. Chemoradiation (CRT) can significantly modify the radiographic appearance of malignant gliomas, especially within the immediate post-CRT period. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this setting, and is thought to be secondary to increased permeability as a byproduct of the complex process of radiation-induced tissue injury, possibly enhanced by temozolomide. We sought to determine whether the addition of a vascular endothelial growth factor (VEGF) signaling inhibitor (cediranib) to conventional CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed glioblastoma before, during, and after CRT. Methods. All patients underwent serial magnetic resonance imaging as part of institutional review board-approved clinical studies. Eleven patients in the control group received only chemoradiation, whereas 29 patients in the study group received chemoradiation and cediranib until disease progression or toxicity. Response assessment was defined according to Response Assessment in Neuro-Oncology criteria, and patients with enlarging lesions were classified into true tumor progressions (TTP) or PsP, based on serial radiographic follow-up. Results. Two patients in the study group (7%) showed signs of apparent early tumor progression, and both were subsequently classified as TTP. Six patients in the control group (54%) showed signs of apparent early tumor progression, and three were subsequently classified as TTP and three as PsP. The frequency of PsP was significantly higher in the control group. Conclusion. Administration of a VEGF inhibitor during and after CRT modifies the expression of PsP by imaging. C1 [Pinho, Marco C.; Polaskova, Pavlina; Kalpathy-Cramer, Jayashree; Jennings, Dominique; Jain, Rakesh K.; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Batchelor, Tracy T.; Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Pinho, Marco C.; Polaskova, Pavlina; Kalpathy-Cramer, Jayashree; Jennings, Dominique; Emblem, Kyrre E.; Rosen, Bruce R.; Sorensen, A. Gregory] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Emblem, Kyrre E.] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Pinho, MC (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM marco.pinho@utsouthwestern.edu RI Emblem, Kyrre/H-6691-2012; OI Emblem, Kyrre/0000-0002-6580-9519; Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Pinho, Marco/0000-0002-4645-1638 FU Harvard Clinical and Translational Science Center [8UL1TR000170-05]; National Institutes of Health [R01CA129371, K24CA125440A, N01CM-2008-00060C, 5R01NS060918, 1U01CA154601, P01-CA080124, 8UL1TR00017005]; Merck; Norwegian Research Council [191088/F20]; South-Eastern Norway Regional Health Authority Grant [2013069] FX This work was conducted with support from the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers); National Institutes of Health R01CA129371 and K24CA125440A (T. T. B.), N01CM-2008-00060Cand5R01NS060918(A. G. S., M. C. P), 1U01CA154601 (B. R. R.), P01-CA080124 (R. K. J), 8UL1TR00017005 and Merck (A. G. S., E. R. G.); and Norwegian Research Council grant 191088/ F20 and South-Eastern Norway Regional Health Authority Grant 2013069 (K. E. E). NR 46 TC 7 Z9 8 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2014 VL 19 IS 1 BP 75 EP 81 DI 10.1634/theoncologist.2013-0101 PG 7 WC Oncology SC Oncology GA 297YP UT WOS:000330291300011 PM 24309981 ER PT J AU Short, NJ Connors, JM AF Short, Nicholas J. Connors, Jean M. TI New Oral Anticoagulants and the Cancer Patient SO ONCOLOGIST LA English DT Article DE Anticoagulants; Direct thrombin inhibitors; Factor Xa inhibitors; Venous thromboembolism; Cancer ID CLINICAL-PRACTICE GUIDELINES; ED AMERICAN-COLLEGE; SYMPTOMATIC VENOUS THROMBOEMBOLISM; PROTHROMBIN COMPLEX CONCENTRATE; MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; FACTOR XA INHIBITOR; ATRIAL-FIBRILLATION; ANTITHROMBOTIC THERAPY; BLEEDING COMPLICATIONS AB Indications for anticoagulation are common in patients with malignancy. Cancer patients have an increased risk of developing venous thromboembolic events or may have other indications for anticoagulation, such as atrial fibrillation. New oral anticoagulants (NOACs) are now available that offer increased options for anticoagulation beyond the traditional vitamin K antagonists and low molecular weight heparins that have long been the cornerstone of treatment. This review will focusonthe threeNOACsthat are currently approved for use in the U.S.: the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors, apixaban and rivaroxaban. Oncologists are likely to encounter an increasing number of patients taking these agents at the time of their cancer diagnosis or to have patients who develop indications for anticoagulation during the course of their disease. The basic pharmacology, current clinical indications, and approach to the use of NOACs in the cancer patient will be reviewed. C1 [Short, Nicholas J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Connors, Jean M.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Connors, Jean M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Connors, JM (reprint author), Brigham & Womens Hosp, Div Hematol, 75 Francis St, Boston, MA 02115 USA. EM jconnors@partners.org OI Short, Nicholas/0000-0002-2983-2738 NR 79 TC 16 Z9 16 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2014 VL 19 IS 1 BP 82 EP 93 DI 10.1634/theoncologist.2013-0239 PG 12 WC Oncology SC Oncology GA 297YP UT WOS:000330291300012 PM 24319019 ER PT J AU Fu, XJ Peng, YB Hu, YP Shi, YZ Yao, M Zhang, X AF Fu, Xiu-Jun Peng, Ying-Bo Hu, Yi-Ping Shi, You-Zhen Yao, Min Zhang, Xiong TI NADPH Oxidase 1 and Its Derived Reactive Oxygen Species Mediated Tissue Injury and Repair SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Review ID VASCULAR SMOOTH-MUSCLE; INTESTINAL EPITHELIAL-CELLS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; NOX FAMILY; HUMAN KERATINOCYTES; NAD(P)H OXIDASES; ANGIOTENSIN-II; GROWTH-FACTOR; MESANGIAL CELLS AB Reactive oxygen species are mostly viewed to cause oxidative damage to various cells and induce organ dysfunction after ischemia-reperfusion injury. However, they are also considered as crucial molecules for cellular signal transduction in biology. NADPH oxidase, whose only function is reactive oxygen species production, has been extensively investigated in many cell types especially phagocytes. The deficiency of NADPH oxidase extends the process of inflammation and delays tissue repair, which causes chronic granulomatous disease in patients. NADPH oxidase 1, one member of the NADPH oxidase family, is not only constitutively expressed in a variety of tissues, but also induced to increase expression in both mRNA and protein levels under many circumstances. NADPH oxidase 1 and its derived reactive oxygen species are suggested to be able to regulate inflammation reaction, cell proliferation and migration, and extracellular matrix synthesis, which contribute to the processes of tissue injury and repair. C1 [Fu, Xiu-Jun; Peng, Ying-Bo; Hu, Yi-Ping; Shi, You-Zhen; Yao, Min] Shanghai Jiao Tong Univ, Sch Med, Inst Traumat Med, Dept Burns & Plast Surg,Peoples Hosp 3, Shanghai 201900, Peoples R China. [Hu, Yi-Ping] Jinan Univ, Hosp 4, Dept Burns, Guangzhou 51022, Guangdong, Peoples R China. [Yao, Min] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Xiong] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Burns & Plast Surg, Shanghai 200025, Peoples R China. RP Zhang, X (reprint author), Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Burns & Plast Surg, Shanghai 200025, Peoples R China. EM xiong@medmail.com.cn FU Ph.D. Programs Foundation of Ministry of Education of China [20120073110088]; Doctoral Innovative Fund at the School of Medicine, Shanghai Jiao Tong University [BXJ201238]; Project of Shanghai "PU JIANG REN CAI" [10PJ1407000] FX This study was supported partially by a Grant from Ph.D. Programs Foundation of Ministry of Education of China (20120073110088), a Grant from the Doctoral Innovative Fund at the School of Medicine, Shanghai Jiao Tong University (BXJ201238), and the Project of Shanghai "PU JIANG REN CAI" (10PJ1407000). NR 75 TC 7 Z9 7 U1 3 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2014 AR 282854 DI 10.1155/2014/282854 PG 10 WC Cell Biology SC Cell Biology GA 303WN UT WOS:000330706000001 ER PT J AU Roghmann, F Sukumar, S Ravi, P Trinh, VQ Meskawi, M Ghani, KR Sammon, JD Friedman, AA Peabody, JO Menon, M Noldus, J Karakiewicz, PI Sun, M Trinh, QD AF Roghmann, Florian Sukumar, Shyam Ravi, Praful Trinh, Vincent Q. Meskawi, Malek Ghani, Khurshid R. Sammon, Jesse D. Friedman, Ariella A. Peabody, James O. Menon, Mani Noldus, Joachim Karakiewicz, Pierre I. Sun, Maxine Quoc-Dien Trinh TI Radical Cystectomy in the Elderly: National Trends and Disparities in Perioperative Outcomes and Quality of Care SO UROLOGIA INTERNATIONALIS LA English DT Article DE Transitional cell carcinoma; Cystectomy; Postoperative complications; Perioperative care ID INVASIVE BLADDER-CANCER; PROPENSITY SCORE; OLDER PATIENTS; SURVIVAL; COMPLICATIONS; COMORBIDITY; POPULATION; AGE; PATTERNS; THERAPY AB Introduction: To examine national trends of radical cystectomy (RC) for urothelial carcinoma of urinary bladder in octogenarian patients and to assess the rates of adverse outcomes. Materials and Methods: Within the Nationwide Inpatient Sample (NIS), we focused on RCs performed between 1998 and 2007. Age was stratified as <80 versus >= 80 years. Propensity-based matched analyses were used to account for treatment selection biases. Generalized linear regression analyses were fitted to predict adverse perioperative events according to age. Results: Of 12,274 RC patients, 1,605 were >= 80 years (13.1%). The RC rates in octogenarians increased significantly from 9.9% in 1998 to 13.7% in 2007. Most elderly patients were treated at low-/intermediate-volume hospitals (81.7%) and nonacademic centers (60.6%). After propensity score matching, the inpatient mortality rate was higher in octogenarians (4.6 vs. 2.6%, p < 0.001). In multivariable analyses, octogenarians were at increased risk of blood transfusions (OR: 1.30) and postoperative complications (OR: 1.22). Conclusions: Most octogenarians undergoing RC are treated at low-/intermediate-volume hospitals and at nonacademic centers. The inpatient hospital mortality is about twice as high in these patients, and adverse perioperative outcomes are more frequent. Such patients may benefit from RC at high-volume and/or academic centers to maximally reduce adverse perioperative outcomes. Copyright (C) 2013 S. Karger AG, Basel C1 [Roghmann, Florian; Trinh, Vincent Q.; Meskawi, Malek; Karakiewicz, Pierre I.; Sun, Maxine; Quoc-Dien Trinh] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Roghmann, Florian; Noldus, Joachim] Ruhr Univ Bochum, Marienhosp, Dept Urol, Herne, Germany. [Sukumar, Shyam; Ravi, Praful; Ghani, Khurshid R.; Sammon, Jesse D.; Friedman, Ariella A.; Peabody, James O.; Menon, Mani; Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Karakiewicz, Pierre I.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Surg,Div Urol, Boston, MA 02115 USA. RP Roghmann, F (reprint author), Canc Prognost & Hlth Outcomes Unit, 264 Blvd Rene Levesque E Suite 228, Montreal, PQ H2X 1P1, Canada. EM f.roghmann@gmail.com OI Friedman, Ariella/0000-0002-0709-0008 NR 31 TC 9 Z9 9 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-1138 EI 1423-0399 J9 UROL INT JI Urol.Int. PY 2014 VL 92 IS 1 BP 27 EP 34 DI 10.1159/000353091 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 302LG UT WOS:000330605400005 PM 24052104 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Applied Anatomy and Physiology of the Spinal Cord SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 3 TC 0 Z9 0 U1 2 U2 4 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 1 EP 9 PG 9 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000001 ER PT J AU Deligiannidis, KM Freeman, MP AF Deligiannidis, Kristina M. Freeman, Marlene P. TI Complementary and alternative medicine therapies for perinatal depression SO BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY LA English DT Article DE complementary; alternative; treatment; S-adenosyl-methionipe; omega-3 fatty acids; St. John's Wort; bright light therapy; acupuncture; exercise; massage; perinatal depression ID RANDOMIZED-CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ST-JOHNS-WORT; MORNING LIGHT THERAPY; POSTPARTUM DEPRESSION; DOUBLE-BLIND; ANTEPARTUM DEPRESSION; HYPERICUM-PERFORATUM; PHYSICAL-ACTIVITY; MASSAGE THERAPY AB Complementary and alternative medicine therapies are increasingly sought out by people with psychiatric disorders. In this chapter, we review the evidence for several commonly used CAM therapies (i.e. omega-3 fatty acids, folate, S-adenosyl-methionine, St John's Wort, bright light therapy, exercise, massage, and acupuncture) in the treatment of perinatal depression. A number of these treatments may be reasonable to consider for women during pregnancy or postpartum, but the safety and efficacy of these relative to standard treatments must still be systematically determined. Evidence-based use of complementary and alternative medicine therapies treatments for perinatal depression is discussed. Adequately powered systematic studies are necessary to determine the role of complementary and alternative medicine therapies in the treatment of perinatal depression. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Deligiannidis, Kristina M.] Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, Depress Specialty Clin, Worcester, MA 01655 USA. [Deligiannidis, Kristina M.] Univ Massachusetts, Mem Med Ctr, Womens Mental Hlth Specialty Clin, Depress Specialty Clin, Worcester, MA 01604 USA. [Freeman, Marlene P.] Massachusetts Gen Hosp, Clin Serv Perinatal & Reprod Psychiat Program, Clin Trials Network, Boston, MA 02114 USA. RP Deligiannidis, KM (reprint author), Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, 328 Shrewsbury St, Worcester, MA 01604 USA. EM kristina.deligiannidis@umassmemorial.org RI Deligiannidis, Kristina/C-3654-2014 OI Deligiannidis, Kristina/0000-0001-7439-2236 FU NCATS NIH HHS [UL1 TR000161]; NIMH NIH HHS [K23 MH097794] NR 97 TC 19 Z9 19 U1 7 U2 37 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6934 EI 1532-1932 J9 BEST PRACT RES CL OB JI Best Pract. Res. Clin. Obstet. Gynaecol. PD JAN PY 2014 VL 28 IS 1 BP 85 EP 95 DI 10.1016/j.bpobgyn.2013.08.007 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 297MC UT WOS:000330258600009 PM 24041861 ER PT J AU Clardy, SM Keliher, EJ Mohan, JF Sebas, M Benoist, C Mathis, D Weissleder, R AF Clardy, Susan M. Keliher, Edmund J. Mohan, James F. Sebas, Matt Benoist, Christophe Mathis, Diane Weissleder, Ralph TI Fluorescent Exendin-4 Derivatives for Pancreatic beta-Cell Analysis SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PEPTIDE-1 RECEPTOR; GLP-1 RECEPTOR; ACTIVATION; ANALOGS AB The ability to reliably identify pancreatic beta-cells would have far reaching implications for a greater understanding of beta-cell biology, measurement of beta-cell mass in diabetes, islet transplantation, and drug development. The glucagon-like peptide-1 receptor (GLP1R) is highly expressed on the surface of insulin producing pancreatic beta-cells. Using systematic modifications of the GLP1R ligand, exendin-4, we screened over 25 compounds and identified a palette of fluorescent exendin-4 with high GLP1R binding affinity. We show considerable differences in affinity, as well as utility of the top candidates for flow cytometry and microscopy of beta-cells. Some of the developed compounds should be particularly useful for basic and translational beta-cell research. C1 [Clardy, Susan M.; Keliher, Edmund J.; Sebas, Matt; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Mohan, James F.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH [PO1 AI54904, T32CA79443] FX We would like to thank Alex Zaltsman and Rainer H. Kohler for assistance with imaging. Part of the work was supported by NIH Grant PO1 AI54904. S.M.C. was supported by an NIH interdisciplinary training grant (T32CA79443). NR 16 TC 16 Z9 16 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2014 VL 25 IS 1 BP 171 EP 177 DI 10.1021/bc4005014 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 294BW UT WOS:000330018400020 PM 24328216 ER PT J AU Jeudin, P Liveright, E del Carmen, MG Perkins, RB AF Jeudin, Patricia Liveright, Elizabeth del Carmen, Marcela G. Perkins, Rebecca B. TI Race, Ethnicity, and Income Factors Impacting Human Papillomayirus Vaccination rates SO CLINICAL THERAPEUTICS LA English DT Review DE ethnicity; HPV; human papillomavirus; income; race; racial disparities; vaccination ID HUMAN-PAPILLOMAVIRUS VACCINATION; GRADE CERVICAL LESIONS; HPV VACCINE; UNITED-STATES; AFRICAN-AMERICAN; YOUNG-WOMEN; ADOLESCENT FEMALES; LATINA MOTHERS; PRIMARY-CARE; SOCIOECONOMIC-STATUS AB Background: Human papillomavirus (HPV) infection and cervical cancer disproportionately affect low-income and minority women. HPV vaccines have the potential to either reduce or exacerbate racial disparities in HPV-related diseases and cervical cancers, depending on the equitability of vaccine uptake. Objectives: This review aims to identify barriers and facilitators of equitable uptake of HPV vaccination among low-income and minority girls. This review discusses factors related to race, ethnicity, and income that are associated with initiation and completion rates of the 3-dose HPV vaccine series and presents targets for intervention. Methods: We reviewed relevant English-language literature to identify current vaccination rates and factors associated with vaccine uptake. Study findings related to race (black, Latino, Asian), and incomes were summarized. Results: Current trends in the United States indicate low uptake among all adolescents, and that rates stagnated between 2011 and 2012. Low-income and minority adolescents are equally or more likely to start the HPV vaccination series than are white and higher-income adolescents, but are less likely to complete all 3 shots. Provider recommendation is a key factor in HPV vaccination, and minorities are less likely to report receiving recommendations for HPV vaccination. Conclusions: As black, Hispanic, and Asian populations continue to grow in the United States over the next several decades, it is imperative that we not only improve HPV vaccination rates overall, but also focus on high-risk populations to prevent an increase in cervical cancer disparities. (C) 2014 Elsevier HS Journals, Inc. All rights reserved. C1 [Jeudin, Patricia; Liveright, Elizabeth; Perkins, Rebecca B.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. RP Perkins, RB (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 85 East Concord St,6th Floor, Boston, MA 02118 USA. EM rebecca.perkins@bmc.org FU American Cancer Society Mentored Research Scholar Grant [MRSG-09-151-01] FX Funding for the research was provided by an American Cancer Society Mentored Research Scholar Grant (MRSG-09-151-01). NR 121 TC 23 Z9 24 U1 4 U2 19 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD JAN PY 2014 VL 36 IS 1 BP 24 EP 37 DI 10.1016/j.clinthera.2013.11.001 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 297KK UT WOS:000330254100005 PM 24417783 ER PT J AU Sukawa, Y Yamarnoto, H Nosho, K Ito, M Igarashi, H Naito, T Mitsuhashi, K Matsunaga, Y Takahashi, T Mikami, M Adachi, Y Suzuki, H Shinomura, Y AF Sukawa, Yasutaka Yamarnoto, Hiroyuki Nosho, Katsuhiko Ito, Miki Igarashi, Hisayoshi Naito, Takafumi Mitsuhashi, Kei Matsunaga, Yasutaka Takahashi, Taiga Mikami, Masashi Adachi, Yasushi Suzuki, Hiromu Shinomura, Yasuhisa TI HER2 Expression and PI3K-Akt Pathway Alterations in Gastric Cancer SO DIGESTION LA English DT Review DE HER2; Gastric cancer; PI3K; Akt; Phosphate and tensin homolog; PIK3CA; Trastuzumab ID BREAST-CANCER; TRASTUZUMAB RESISTANCE; COLORECTAL-CANCER; PIK3CA MUTATIONS; RECEPTOR; GROWTH; CELLS; PTEN; ASSOCIATION; CONTRIBUTES AB The anti-HER2 antibody trastuzumab has led to an era of personalized therapy in gastric cancer (GC). As a result, HER2 expression has become a major concern in GC. HER2 overexpression is seen in 7-34% of GC cases. Trastuzumab is an antibody that targets the HER2 extracellular domain and induces antibody-dependent cellular cytotoxicity and inhibition of the HER2 downstream signals. Mechanisms of resistance to trastuzumab have been reported in breast cancer. There are various mechanisms underlying trastuzumab resistance, such as alterations of HER2 structure or surroundings, dysregulation of HER2 downstream signal effectors and interaction of HER2 with other membrane receptors. The PI3K-Akt pathway is one of the main downstream signaling pathways of HER2. It is well known that PIK3CA mutations and phosphate and tensin homolog (PTEN) inactivation cause over-activation of the downstream signal without an upstream signal activation. Frequencies of PIK3CA mutations and PTEN inactivation have been reported to be 4-25 and 16-77%, respectively. However, little is known about the association between HER2 expression and PI3K-Akt pathway alterations in GC. We have found that HER2 overexpression was significantly correlated with pAkt expression in GC tissues. Furthermore, pAkt expression was correlated with poor prognosis. These results suggest that the PI3K-Akt pathway plays an important role in HER2-positive GC. Moreover, PIK3CA mutations and/or PTEN inactivation might affect the effectiveness of HER2-targeting therapy. Hence, it is necessary to clarify not only HER2 alterations but also PI3K-Akt pathway alterations for HER2-targeting therapy in GC. This review will introduce recent investigations and consider the current status of HER2-targeted therapy for treatment of GC. (C) 2014 S. Karger AG, Basel C1 [Sukawa, Yasutaka; Nosho, Katsuhiko; Ito, Miki; Igarashi, Hisayoshi; Naito, Takafumi; Mitsuhashi, Kei; Matsunaga, Yasutaka; Takahashi, Taiga; Mikami, Masashi; Adachi, Yasushi; Shinomura, Yasuhisa] Sapporo Med Univ, Sch Med, Dept Gastroenterol, Dept Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. [Suzuki, Hiromu] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido, Japan. [Yamarnoto, Hiroyuki] St Marianna Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan. RP Sukawa, Y (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM yasutaka_sukawa@dfci.harvard.edu NR 30 TC 20 Z9 22 U1 5 U2 20 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 EI 1421-9867 J9 DIGESTION JI Digestion PY 2014 VL 89 IS 1 SI SI BP 12 EP 17 DI 10.1159/000356201 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 295YI UT WOS:000330151900003 PM 24458107 ER PT J AU Gougeon, R Sievenpiper, JL Jenkins, D Yale, JF Bell, R Despres, JP Ransom, TPP Camelon, K Dupre, J Kendall, C Hegazi, RA Marchetti, A Hamdy, O Mechanick, JI AF Gougeon, Rejeanne Sievenpiper, John L. Jenkins, David Yale, Jean-Francois Bell, Rhonda Despres, Jean-Pierre Ransom, Thomas P. P. Camelon, Kathryn Dupre, John Kendall, Cyril Hegazi, Refaat A. Marchetti, Albert Hamdy, Osama Mechanick, Jeffrey I. TI The Transcultural Diabetes Nutrition Algorithm: A Canadian Perspective SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Article ID LOW-GLYCEMIC-INDEX; RANDOMIZED CONTROLLED-TRIAL; ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY; CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE; ENERGY-EXPENDITURE; GLUCOSE-TOLERANCE; DIETARY-EDUCATION; COLLEGE ALUMNI AB The Transcultural Diabetes Nutrition Algorithm (tDNA) is a clinical tool designed to facilitate implementation of therapeutic lifestyle recommendations for people with or at risk for type 2 diabetes. Cultural adaptation of evidence-based clinical practice guidelines (CPG) recommendations is essential to address varied patient populations within and among diverse regions worldwide. The Canadian version of tDNA supports and targets behavioural changes to improve nutritional quality and to promote regular daily physical activity consistent with Canadian Diabetes Association CPG, as well as channelling the concomitant management of obesity, hypertension, dyslipidemia, and dysglycaemia in primary care. Assessing glycaemic index (GI) (the ranking of foods by effects on postprandial blood glucose levels) and glycaemic load (GL) (the product of mean GI and the total carbohydrate content of a meal) will be a central part of the Canadian tDNA and complement nutrition therapy by facilitating glycaemic control using specific food selections. This component can also enhance other metabolic interventions, such as reducing the need for antihyperglycaemic medication and improving the effectiveness of weight loss programs. This tDNA strategy will be adapted to the cultural specificities of the Canadian population and incorporated into the tDNA validation methodology. C1 [Gougeon, Rejeanne] Royal Victoria Hosp, McGill Univ Hlth Ctr, Crabtree Nutr Labs, Montreal, PQ H3H 1A1, Canada. [Sievenpiper, John L.] McMaster Univ, Fac Hlth Sci, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada. [Sievenpiper, John L.] St Michaels Hosp, Clin Nutr & Risk Factor Modificat Ctr, Toronto Knowledge Synth & Clin Trials Unit 3D, Toronto, ON M5C 2T2, Canada. [Jenkins, David] Univ Toronto, Fac Med, Dept Nutr Sci & Med, Toronto, ON M5S 3E2, Canada. [Jenkins, David] St Michaels Hosp, Div Endocrinol & Metab, Clin Nutr & Risk Factor Modificat Ctr, Toronto, ON M5C 2T2, Canada. [Jenkins, David] St Michaels Hosp, Div Endocrinol & Metab, Li Ka Shing Knowledge Inst, Toronto, ON M5C 2T2, Canada. [Yale, Jean-Francois] Royal Victoria Hosp, McGill Univ Hlth Ctr, Montreal, PQ H3A 1A1, Canada. [Bell, Rhonda] Univ Alberta, Div Agr Food & Nutr Sci, Div Human Nutr, Edmonton, AB T6G 2E1, Canada. [Bell, Rhonda] Univ Alberta, Alberta Diabet Inst, Edmonton, AB T6G 2E1, Canada. [Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada. [Despres, Jean-Pierre] Univ Laval, Fac Med, Dept Kinesiol, Ste Foy, PQ G1V 4G5, Canada. [Ransom, Thomas P. P.] Capital Hlth, Div Endocrinol & Metab, Halifax, NS B3H 2Y9, Canada. [Ransom, Thomas P. P.] Dalhousie Univ, Halifax, NS B3H 3J5, Canada. [Camelon, Kathryn] Univ Hlth Network, Dept Allied Hlth, Toronto, ON M5G 2C4, Canada. [Dupre, John] Univ Western Ontario, Robarts Res, London, ON N6A 5B7, Canada. [Kendall, Cyril] St Michaels Hosp, Clin Nutr & Risk Factor Modificat Ctr, Toronto, ON M5S 3E2, Canada. [Kendall, Cyril] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON, Canada. [Kendall, Cyril] Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK, Canada. [Hegazi, Refaat A.] Abbott Labs, Abbott Pk, IL USA. [Marchetti, Albert] Med Educ & Res Alliance Med ERA, New York, NY 10019 USA. [Marchetti, Albert] Univ Med & Dent New Jersey, Dept Prevent Med & Community Hlth, Newark, NJ 07101 USA. [Hamdy, Osama] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02215 USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP Gougeon, R (reprint author), Royal Victoria Hosp, McGill Univ Hlth Ctr, Crabtree Nutr Labs, H6-90,687 Pine Ave West, Montreal, PQ H3H 1A1, Canada. EM rejeanne.gougeon@muhc.mcgill.ca FU Abbott Nutrition International; Sanofi; Eli Lilly; NovoNordisk; Merck; Bristol-Myers Squibb; Astra Zeneca; Boehringer Ingelheim; Janssen; Medtronic; Abbott; Takeda; GlaxoSmithKline; Merck Co.; Novartis; Bristal-Myers Squibb; AstraZeneca; Novo Nordisk; Sanofi-Aventis; Abbott Nutrition FX Financial support was provided by Abbott Nutrition International. Other support may have been provided to task force members as follows. Jean-Francois Yale has received financial support for advisory boards, lectures, and research from Sanofi, Eli Lilly, NovoNordisk, Merck, Bristol-Myers Squibb, Astra Zeneca, Boehringer Ingelheim, Janssen, Medtronic, Abbott, Takeda, and GlaxoSmithKline. Thomas PP Ransom has received financial support for advisory boards, lectures and research from Merck & Co., Novartis, Boehringer Ingelheim, Bristal-Myers Squibb, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk and Sanofi-Aventis. Jean-Pierre Despres declares associations with the following companies: Abbott, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Pfizer Canada, Sanofi, Theratechnologies, and Torrent Pharmaceuticals.; Cyril Kendall has received research grants, travel funding, consultant fees, and honoraria, or has served on the scientific advisory board for Abbott Laboratories, Advanced Food Materials Network, Agrifood and Agriculture Canada ( AAFC), Almond Board of California, American Peanut Council, American Pistachio Growers, Barilla, California Strawberry Commission, Calorie Control Council, Canadian Institutes of Health Research (CIHR), Canola Council of Canada, The Coca Cola Company ( investigator initiated, unrestricted), Danone, General Mills, Hain Celestial, International Tree Nut Council, Kellogg, Kraft, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Orafti, Paramount Farms, Peanut Institute, Pepsi-Co, Pulse Canada, Saskatchewan Pulse Growers, Solae, Sun-Maid, Tate entific Advisory Board of Sanitarium Company, Agriculture and Agrifood Canada (AAFC), Canadian Agriculture Policy Institute (CAPI), Loblaw Supermarket, Herbal Life International, Nutritional Fundamental for Health, Pacific Health Laboratories, Metagenics, Bayer Consumer Care, Orafti, Dean Foods, Kellogg's, Quaker Oats, Procter & Gamble, Coca-Cola, NuVal Griffin Hospital, Abbott, Pulse Canada, Saskatchewan Pulse Growers, and Canola Council of Canada; received honoraria for scientific advice from Sanitarium Company, Orafti, the Almond Board of California, the American Peanut Council, International Tree Nut Council Nutrition Research and Education Foundation and the Peanut Institute, Herbal Life International, Pacific Health Laboratories, Nutritional Fundamental for Health, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Oldways, Kellogg's, Quaker Oats, Procter & Gamble, Coca-Cola, NuVal Griffin Hospital, Abbott, Canola Council of Canada, Dean Foods, California Strawberry Commission, Hain Celestial, Pepsi, and Alpro Foundation; has been on the speakers panel for the Almond Board of California; received research grants from Saskatchewan Pulse Growers, the Agricultural Bioproducts Innovation Program (ABIP) through the Pulse Research Network (PURENet), Advanced Food Materials Network (AFMNet), Loblaw, Unilever, Barilla, Almond Board of California, Coca-Cola, Solae, Haine Celestial, Sanitarium Company, Orafti, International Tree Nut Council Nutrition Research and Education Foundation and the Peanut Institute, the Canola and Flax Councils of Canada, Calorie Control Council, Canadian Institutes of Health Research, Canada Foundation for Innovation, and the Ontario Research Fund; and received travel support to meetings from the Solae, Sanitarium Company, Orafti, AFMNet, Coca-Cola, The Canola and Flax Councils of Canada, Oldways Preservation Trust, Kellogg's, Quaker Oats, Griffin Hospital, Abbott Laboratories, Dean Foods, the California Strawberry Commission, American Peanut Council, Herbal Life International, Nutritional Fundamental for Health, Metagenics, Bayer Consumer Care, AAFC, CAPI, Pepsi, Almond Board of California, Unilever, Alpro Foundation, International Tree Nut Council, Barilla, Pulse Canada, and the Saskatchewan Pulse Growers. Dr Jenkins' wife is a Director of Glyceamic Index Laboratories, Toronto, Ontario, Canada. Albert Marchetti has received financial support for research and the development of educational materials in diabetes from Eli Lilly, Takeda, GlaxoSmithKline, Bristol-Myers Squibb, and Abbott Nutrition International. Osama Hamdy has received financial support as a Consultant from Abbott Nutrition and as a Speaker from Amylin/Eli Lilly and Abbott Nutrition.; Jeffery I Mechanick has received honoraria for lectures and program development from Abbott Nutrition International. NR 48 TC 1 Z9 1 U1 1 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2014 AR 151068 DI 10.1155/2014/151068 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299IE UT WOS:000330388600001 ER PT J AU Goldfine, AB Vernon, A Zinner, M AF Goldfine, Allison B. Vernon, Ashley Zinner, Michael TI Where Are the Health Care Cost Savings With Bariatric Surgery in Obesity Management? SO JAMA SURGERY LA English DT Editorial Material ID GASTRIC BYPASS; MORTALITY; INTERVENTION C1 [Goldfine, Allison B.] Brigham & Womens Hosp, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. [Goldfine, Allison B.; Vernon, Ashley; Zinner, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Vernon, Ashley; Zinner, Michael] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Goldfine, AB (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [R56DK095451, RC1DK086918, P30 DK03836] NR 12 TC 2 Z9 2 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JAN PY 2014 VL 149 IS 1 BP 5 EP 6 DI 10.1001/jamasurg.2013.3060 PG 2 WC Surgery SC Surgery GA 295LJ UT WOS:000330117300001 PM 24195967 ER PT J AU Trinh, VQ Karakiewicz, PI Sammon, J Sun, M Sukumar, S Gervais, MK Shariat, SF Tian, Z Kim, SP Kowalczyk, KJ Hu, JC Menon, M Trinh, QD AF Trinh, Vincent Q. Karakiewicz, Pierre I. Sammon, Jesse Sun, Maxine Sukumar, Shyam Gervais, Mai-Kim Shariat, Shahrokh F. Tian, Zhe Kim, Simon P. Kowalczyk, Keith J. Hu, Jim C. Menon, Mani Quoc-Dien Trinh TI Venous Thromboembolism After Major Cancer Surgery Temporal Trends and Patterns of Care SO JAMA SURGERY LA English DT Article ID FATAL PULMONARY-EMBOLISM; DEEP-VEIN THROMBOSIS; HOSPITALIZED-PATIENTS; BLACK-AMERICANS; CLAIMS DATA; VOLUME; RISK; VTE; ASSOCIATION; PREVENTION AB IMPORTANCE There is limited data on the prevalence and mortality of venous thromboembolism (VTE) following oncologic surgery. OBJECTIVE To evaluate the trends, factors, and mortality of VTE following major cancer surgery. DESIGN, SETTING, AND PARTICIPANTS Patients undergoing colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy, or prostatectomy were identified retrospectively using the Nationwide Inpatient Sample between January 1, 1999, and December 30, 2009, resulting in a weighted estimate of 2 508 916 patients. MAIN OUTCOMES AND MEASURES Venous thromboembolism following major cancer surgery was assessed according to date, patient, and hospital characteristics. The determinants of in-hospital VTE were evaluated using logistic regression analysis. RESULTS Venous thromboembolism showed an estimated annual percentage increase of 4.0% (95% CI, 2.9% to 5.1%), which contrasts with a 2.4%(95% CI, -4.3% to -0.5%) annual decrease in mortality in VTE after major cancer surgery. In multivariate logistic regression analysis, older age (odds ratio [OR], 1.03; P < .001), female sex (OR, 1.25; P < .001), black race (vs white; OR, 1.56; P < .001), Charlson comorbidity index score of 3 or more (OR, 1.85; P <.001), and Medicaid (vs private insurance; OR, 2.04; P < .001), Medicare (OR, 1.39; P <.001), and uninsured (OR, 1.49; P < .001) status were associated with an increased risk of VTE. Conversely, other (nonwhite and nonblack) race (OR, 0.75; P < .001) was associated with a lower risk of VTE. Among hospital characteristics, urban location (OR, 1.32; P < .001) and teaching status (OR, 1.08; P = .01) were associated with greater odds of VTE. Patients with vs without VTE experienced 5.3-fold greater odds of mortality. CONCLUSIONS AND RELEVANCE During our study period, VTE events following major cancer surgery increased in frequency; however, associated VTE mortality decreased. Changing VTE detection guidelines and better management of this condition may explain our findings. C1 [Trinh, Vincent Q.; Karakiewicz, Pierre I.; Sun, Maxine; Tian, Zhe] Univ Montreal, Canc Prognost & Hlth Outcomes Unit, Ctr Hlth, Montreal, PQ, Canada. [Sammon, Jesse; Sukumar, Shyam; Menon, Mani] VUI Ctr Outcomes Res Analyt & Evaluat, Henry Ford Hlth Syst, Detroit, MI USA. [Gervais, Mai-Kim] Univ Montreal, Div Gen Surg, Ctr Hlth, Montreal, PQ, Canada. [Shariat, Shahrokh F.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA. [Kim, Simon P.] Yale Univ, Sch Med, Dept Urol, New Haven, CT USA. [Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Urol Surg, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 45 Francis St,ASB II-3, Boston, MA 02115 USA. EM trinh.qd@gmail.com FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre Foundation FX This study was partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery, and the University of Montreal Health Centre Foundation (Dr Karakiewicz). NR 33 TC 23 Z9 23 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JAN PY 2014 VL 149 IS 1 BP 43 EP 49 DI 10.1001/jamasurg.2013.3172 PG 7 WC Surgery SC Surgery GA 295LJ UT WOS:000330117300009 PM 24197279 ER PT J AU Zhang, HL Wang, MB Wu, LM Zhang, HN Jin, T Wu, J Sun, L AF Zhang, Hongliang Wang, Meibo Wu, Limin Zhang, Haining Jin, Tao Wu, Jiang Sun, Li TI Novel prion protein gene mutation at codon 196 (E196A) in a septuagenarian with Creutzfeldt-Jakob disease SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Codon 196; Creutzfeldt-Jakob disease; Mutation; Prion AB Creutzfeldt-Jakob disease (CJD) is a rare and rapidly progressive neurodegenerative disease of the central nervous system, which may occur in inherited, acquired (variant and iatrogenic), or spontaneous (sporadic) forms. We report a 76-year-old Chinese man with CJD found to have a novel mutation in the prion protein gene (PRNP). The 14-3-3 protein was positive in the cerebrospinal fluid; diffusion-weighted MRI revealed ribbon-like high signal intensity in the bilateral cortices; and electroencephalography showed typical periodic synchronous discharge. CJD was diagnosed based on characteristic clinical manifestations. Interestingly, a point mutation of PRNP at codon 196 (E196A: GAG -> GCG) was detected. In conclusion, we identified a patient with CJD with a novel PRNP mutation, which expands the spectrum of PRNP mutations in CJD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Zhang, Hongliang; Wang, Meibo; Wu, Limin; Zhang, Haining; Jin, Tao; Wu, Jiang; Sun, Li] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130021, Peoples R China. [Wang, Meibo] Tengzhou Cent Peoples Hosp, Dept Neurol, Tengzhou, Peoples R China. [Wu, Limin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Cambridge, MA 02138 USA. RP Sun, L (reprint author), Jilin Univ, Hosp 1, Dept Neurol, 71 Xinmin St, Changchun 130021, Peoples R China. EM sjnksunli@163.com FU National Natural Science Foundation of China [81241147] FX The work was supported by grants from the National Natural Science Foundation of China (No. 81241147). NR 7 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JAN PY 2014 VL 21 IS 1 BP 175 EP 178 DI 10.1016/j.jocn.2013.03.016 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 295XO UT WOS:000330149900039 PM 23787189 ER PT J AU Denlinger, CS Ligibel, J AF Denlinger, Crystal S. Ligibel, Jennifer TI A Work in Progress: Developing the New NCCN Guidelines for Survivorship SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID CANCER SURVIVORS; CARE C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Ligibel, Jennifer] Dana Farber Canc Inst, Womens Canc Program, Boston, MA USA. [Ligibel, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ligibel, Jennifer] NCI, Transdisciplinary Res Energet & Canc Initiat, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2014 VL 12 IS 1 BP 1 EP 4 PG 4 WC Oncology SC Oncology GA 298OG UT WOS:000330333200001 PM 24453287 ER PT J AU Coccia, PF Pappo, AS Altman, J Bhatia, S Borinstein, SC Flynn, J Frazier, AL George, S Goldsby, R Hayashi, R Huang, MS Johnson, RH Beaupin, LK Link, MP Oeffinger, KC Orr, KM Reed, D Spraker, HL Thomas, DA von Mehren, M Wechsler, DS Whelan, KF Zebrack, B Shead, DA Sundar, H AF Coccia, Peter F. Pappo, Alberto S. Altman, Jessica Bhatia, Smita Borinstein, Scott C. Flynn, Joseph Frazier, A. Lindsay George, Suzanne Goldsby, Robert Hayashi, Robert Huang, Mary S. Johnson, Rebecca H. Beaupin, Lynda Kwon Link, Michael P. Oeffinger, Kevin C. Orr, Kathleen M. Reed, Damon Spraker, Holly L. Thomas, Deborah A. von Mehren, Margaret Wechsler, Daniel S. Whelan, Kimberly F. Zebrack, Brad Shead, Dorothy A. Sundar, Hema TI Adolescent and Young Adult Oncology, Version 2.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PREMATURE OVARIAN FAILURE; CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; HODGKIN-STUDY-GROUP; BREAST-CANCER; FERTILITY PRESERVATION; HORMONE AGONIST; REVERSIBLE CONTRACEPTION; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN AB The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss the fertility and endocrine issues that are relevant to the management of AYA patients with cancer. Fertility preservation should be an essential part in the treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion of fertility preservation and contraception before the start of treatment. Oophoropexy and embryo cryopreservation are the 2 established options for fertility preservation in women. Semen cryopreservation before the start of treatment is the most reliable and well-established method of preserving fertility in men. AYA women with cancer also have unique contraception needs, depending on the type of cancer, its treatment, and treatment-related complications. Management of cancer during pregnancy poses significant diagnostic and therapeutic challenges for both the patient and the physician. AYA women diagnosed with cancer during pregnancy require individualized treatment from a multidisciplinary team involving medical, surgical, radiation, and gynecologic oncologists; obstetricians; and perinatologists. C1 [Coccia, Peter F.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE 68198 USA. [Pappo, Alberto S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Altman, Jessica] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Bhatia, Smita] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Borinstein, Scott C.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Flynn, Joseph] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Flynn, Joseph] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [Frazier, A. Lindsay; George, Suzanne] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Goldsby, Robert] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Hayashi, Robert] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Hayashi, Robert] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Huang, Mary S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Johnson, Rebecca H.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Beaupin, Lynda Kwon] Roswell Pk Canc Inst, Buffalo, NY USA. [Link, Michael P.] Stanford Canc Inst, Stanford, CA USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Orr, Kathleen M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Reed, Damon] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Spraker, Holly L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Thomas, Deborah A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA USA. [Wechsler, Daniel S.] Duke Canc Inst, Durham, NC USA. [Whelan, Kimberly F.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Zebrack, Brad] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Shead, Dorothy A.; Sundar, Hema] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Coccia, PF (reprint author), Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE 68198 USA. FU Bayer HealthCare; Onyx Pharmaceuticals, Inc.; Algeta US; Exelixis, Inc.; Genentech USA, Inc.; Merck Sharp Dohme Corp; NOVOCURE Ltd.; Prometheus Laboratories Inc. FX Supported by educational grants from Bayer HealthCare, Onyx Pharmaceuticals, Inc., and Algeta US; Exelixis, Inc.; Genentech USA, Inc.; Merck Sharp & Dohme Corp; NOVOCURE Ltd.; and Prometheus Laboratories Inc. NR 70 TC 28 Z9 28 U1 1 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2014 VL 12 IS 1 BP 21 EP 32 PG 12 WC Oncology SC Oncology GA 298OG UT WOS:000330333200004 PM 24453290 ER PT J AU Seah, DSE Luis, IV Macrae, E Sohl, J Litsas, G Winer, EP Lin, NU Burstein, HJ AF Seah, Davinia S. E. Luis, Ines Vaz Macrae, Erin Sohl, Jessica Litsas, Georgia Winer, Eric P. Lin, Nancy U. Burstein, Harold J. TI Use and Duration of Chemotherapy in Patients With Metastatic Breast Cancer According to Tumor Subtype and Line of Therapy SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID MONOCLONAL-ANTIBODIES; MOLECULAR PORTRAITS; CLINICAL-OUTCOMES; 2 DECADES; SURVIVAL; TRIALS; WOMEN; TRASTUZUMAB; RECURRENCE; ERIBULIN AB Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR) positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR+, TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR+ breast cancer, and 17 months for TNBC (P<.0001). Patients with HER2-amplified disease received the most lines (median, 4; P..032) and the longest duration of chemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR+ and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study. C1 [Seah, Davinia S. E.; Luis, Ines Vaz; Sohl, Jessica; Litsas, Georgia; Winer, Eric P.; Lin, Nancy U.; Burstein, Harold J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Macrae, Erin] Ohio State Univ, Coll Med, Dept Med Oncol, Columbus, OH 43210 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, 450 Brookline Ave, Boston, MA 02215 USA. EM hal_burstein@dfci.harvard.edu FU Metastatic Research Fund; Megan Lally Memorial Fund; Susan G. Komen for the Cure; Genentech, Inc.; GlaxoSmithKline; Novartis FX This work was supported by the Metastatic Research Fund (anonymous donor to Drs. Winer and Lin), Megan Lally Memorial Fund, and Susan G. Komen for the Cure (Dr. Winer). Dr. Lin has disclosed that she received research funding from Genentech, Inc., GlaxoSmithKline, and Novartis. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. NR 37 TC 6 Z9 6 U1 1 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2014 VL 12 IS 1 BP 71 EP 80 PG 10 WC Oncology SC Oncology GA 298OG UT WOS:000330333200008 PM 24453294 ER PT J AU Hurria, A Wildes, T Blair, SL Browner, IS Cohen, HJ deShazo, M Dotan, E Edil, BH Extermann, M Ganti, AKP Holmes, HM Jagsi, R Karlekar, MB Keating, NL Korc-Grodzicki, B McKoy, JM Medeiros, BC Mrozek, E O'Connor, T Rugo, HS Rupper, RW Silliman, RA Stirewalt, DL Tew, WP Walter, LC Weir, AB Bergman, MA Sundar, H AF Hurria, Arti Wildes, Tanya Blair, Sarah L. Browner, Ilene S. Cohen, Harvey Jay deShazo, Mollie Dotan, Efrat Edil, Barish H. Extermann, Martine Ganti, Apar Kishor P. Holmes, Holly M. Jagsi, Reshma Karlekar, Mohana B. Keating, Nancy L. Korc-Grodzicki, Beatriz McKoy, June M. Medeiros, Bruno C. Mrozek, Ewa O'Connor, Tracey Rugo, Hope S. Rupper, Randall W. Silliman, Rebecca A. Stirewalt, Derek L. Tew, William P. Walter, Louise C. Weir, Alva B., III Bergman, Mary Anne Sundar, Hema TI Senior Adult Oncology, Version 2.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ACUTE MYELOID-LEUKEMIA; COMPREHENSIVE GERIATRIC ASSESSMENT; ACUTE LYMPHOBLASTIC-LEUKEMIA; ELDERLY CANCER-PATIENTS; INAPPROPRIATE MEDICATION USE; RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; QUALITY-OF-LIFE; RISK MYELODYSPLASTIC SYNDROMES; PREDNISONE PLUS THALIDOMIDE AB Cancer is the leading cause of death in older adults aged 60 to 79 years. The biology of certain cancers and responsiveness to therapy changes with the patient's age. Advanced age alone should not preclude the use of effective treatment that could improve quality of life or extend meaningful survival. The challenge of managing older patients with cancer is to assess whether the expected benefits of treatment are superior to the risk in a population with decreased life expectancy and decreased tolerance to stress. These guidelines provide an approach to decision-making in older cancer patients based on comprehensive geriatric assessment and also include diseasespecific issues related to age in the management of some cancer types in older adults. C1 [Hurria, Arti] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Wildes, Tanya] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Wildes, Tanya] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Blair, Sarah L.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Browner, Ilene S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Cohen, Harvey Jay] Duke Canc Inst, Durham, NC USA. [deShazo, Mollie] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Dotan, Efrat] Fox Chase Canc Ctr, Philadelphia, PA USA. [Edil, Barish H.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Extermann, Martine] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Ganti, Apar Kishor P.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Holmes, Holly M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Jagsi, Reshma] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Karlekar, Mohana B.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Keating, Nancy L.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Korc-Grodzicki, Beatriz; Tew, William P.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [McKoy, June M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Medeiros, Bruno C.] Stanford Canc Inst, Stanford, CA USA. [Mrozek, Ewa] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Mrozek, Ewa] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY USA. [Rugo, Hope S.; Walter, Louise C.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Rupper, Randall W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Silliman, Rebecca A.] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Stirewalt, Derek L.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Weir, Alva B., III] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Bergman, Mary Anne; Sundar, Hema] NCCN, Ft Washington, PA USA. RP Hurria, A (reprint author), City Hope Comprehens Canc Ctr, Duarte, CA USA. RI Mrozek, Ewa/E-3708-2011 NR 298 TC 32 Z9 34 U1 11 U2 16 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2014 VL 12 IS 1 BP 82 EP 126 PG 45 WC Oncology SC Oncology GA 298OG UT WOS:000330333200009 PM 24453295 ER PT J AU Jaaskelainen, IP Ahveninen, J AF Jaaskelainen, Iiro P. Ahveninen, Jyrki TI Auditory-Cortex Short-Term Plasticity Induced by Selective Attention SO NEURAL PLASTICITY LA English DT Review ID SPECTROTEMPORAL RECEPTIVE-FIELDS; TONOTOPIC ORGANIZATION; HUMAN BRAIN; MACAQUE MONKEY; RHESUS-MONKEY; FUNCTIONAL SPECIALIZATION; EVOKED-POTENTIALS; SINGLE NEURONS; BELT CORTEX; FREQUENCY AB The ability to concentrate on relevant sounds in the acoustic environment is crucial for everyday function and communication. Converging lines of evidence suggests that transient functional changes in auditory-cortex neurons, "short-term plasticity", might explain this fundamental function. Under conditions of strongly focused attention, enhanced processing of attended sounds can take place at very early latencies (similar to 50 ms from sound onset) in primary auditory cortex and possibly even at earlier latencies in subcortical structures. More robust selective-attention short-term plasticity is manifested as modulation of responses peaking at similar to 100 ms from sound onset in functionally specialized nonprimary auditory-cortical areas by way of stimulus-specific reshaping of neuronal receptive fields that supports filtering of selectively attended sound features from task-irrelevant ones. Such effects have been shown to take effect in similar to seconds following shifting of attentional focus. There are findings suggesting that the reshaping of neuronal receptive fields is even stronger at longer auditory-cortex response latencies (similar to 300 ms from sound onset). These longer-latency short-term plasticity effects seem to build up more gradually, within tens of seconds after shifting the focus of attention. Importantly, some of the auditory-cortical short-term plasticity effects observed during selective attention predict enhancements in behaviorally measured sound discrimination performance. C1 [Jaaskelainen, Iiro P.] Aalto Univ, Brain & Mind Lab, Dept Biomed Engn & Computat Sci, Sch Sci, Espoo 00076, Aalto, Finland. [Ahveninen, Jyrki] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Ahveninen, Jyrki] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Jaaskelainen, IP (reprint author), Aalto Univ, Brain & Mind Lab, Dept Biomed Engn & Computat Sci, Sch Sci, Espoo 00076, Aalto, Finland. EM iiro.jaaskelainen@aalto.fi RI Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 FU Academy of Finland; National Institutes of Health [R01MH083744, R21DC010060, R01HD040712, R01NS037462, 5R01EB009048, P41RR14075] FX This work was supported by the Academy of Finland and the National Institutes of Health Awards R01MH083744, R21DC010060, R01HD040712, R01NS037462, 5R01EB009048, and P41RR14075. NR 111 TC 1 Z9 1 U1 2 U2 11 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2014 AR 216731 DI 10.1155/2014/216731 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 299IF UT WOS:000330388700001 ER PT J AU Degani-Costa, LH Faresin, SM Falcao, LFD AF Degani-Costa, Luiza Helena Faresin, Sonia Maria dos Reis Falcao, Luiz Fernando TI Preoperative evaluation of a lung disease patient SO REVISTA BRASILEIRA DE ANESTESIOLOGIA LA Portuguese DT Article ID BRACHIAL-PLEXUS BLOCK; PULMONARY-FUNCTION CHANGES; OBSTRUCTIVE SLEEP-APNEA; RESIDUAL NEUROMUSCULAR BLOCKADE; MULTIFACTORIAL RISK INDEX; MAJOR NONCARDIAC SURGERY; POSTANESTHESIA CARE-UNIT; ABDOMINAL-SURGERY; SURGICAL-PATIENTS; POSTOPERATIVE COMPLICATIONS C1 [Degani-Costa, Luiza Helena; Faresin, Sonia Maria; dos Reis Falcao, Luiz Fernando] Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil. [Degani-Costa, Luiza Helena; dos Reis Falcao, Luiz Fernando] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Falcao, LFD (reprint author), Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil. EM luizfernandofalcao@gmail.com NR 104 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0034-7094 EI 1806-907X J9 REV BRAS ANESTESIOL JI Rev. Bras. Anestesiol. PD JAN-FEB PY 2014 VL 64 IS 1 BP 22 EP 34 PG 13 WC Anesthesiology SC Anesthesiology GA 295LT UT WOS:000330118300003 ER PT J AU Rowland, NC Miller, KJ Starr, PA AF Rowland, Nathan C. Miller, Kai J. Starr, Philip A. TI Three-Dimensional Accuracy of ECOG Strip Electrode Localization Using Coregistration of Preoperative MRI and Intraoperative Fluoroscopy SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Coregistration; Fluoroscopic radiography; Magnetic resonance imaging; Normalized mutual information; Statistical parametric mapping; X-ray radiography ID DEEP BRAIN-STIMULATION; SUBDURAL ELECTRODES; IMPLANTED ELECTRODES; SENSORIMOTOR CORTEX; PARKINSONS-DISEASE; FOCAL EPILEPSY AB Background/Aims: Algorithms that estimate implanted cortical strip electrode coordinates using postoperative skull X-ray coregistration with preoperative magnetic resonance imaging (MRI) have been proposed. However, when cortical strip electrodes are inserted for temporary use and removed prior to closure, intraoperative imaging either fluoroscopy or computed tomography (CT) must be substituted. Objectives:To measure the accuracy of temporarily inserted su bdural strip electrode coordinates using intraoperative fluoroscopic coregistration with preoperative MRI compared to intraoperative CT coregistration with preoperative MRI. Methods: In 5 patients undergoing movement disorder surgery, preoperative MRI was used to generate a three-dimensional cortical surface manually scaled to fit an intraoperative skull fluorogrann with an in situ six-contact subdural electrode strip. Individual contact coordinates were estimated using subjacent gyral and sulcal patterns. Estimated co- ordinates were compared to reference coordinates obtained by preoperative MRI coregistration with intraoperative CT in the same patients. Results: Mean electrode coordinate distances between estimated and reference locations were 6.0 +/- 0.8 (x-axis, mediolateral), 3.3 +/- 0.5 (y-axis, anterior-posterior) and 4.0 +/- 0.5 mm (z-axis, superior-inferior; n = 30). Conclusions: Localization of temporarily inserted subdural electrodes can be accomplished using preoperative MRI and intraoperative fluoroscopy. The accuracy of this approach is verified by preoperative MRI and intraoperative CT coregistration in the same patients. (C) 2013 S. Karger AG, Basel C1 [Rowland, Nathan C.; Starr, Philip A.] Univ Calif San Francisco, UCSF Surg Movement Disorders Ctr, San Francisco, CA 94143 USA. [Starr, Philip A.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Neurol Surg, San Francisco, CA 94143 USA. [Miller, Kai J.] Stanford Univ, Sch Med, Dept Neurosurg, Palo Alto, CA 94304 USA. RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M-779, San Francisco, CA 94143 USA. EM StarrP@neurosurg.ucsf.edu NR 23 TC 1 Z9 1 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 EI 1423-0372 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2014 VL 92 IS 1 BP 8 EP 16 DI 10.1159/000350027 PG 9 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 295YH UT WOS:000330151800002 PM 24216603 ER PT J AU Vaid, M Singh, T Prasad, R Katiyar, SK AF Vaid, Mudit Singh, Tripti Prasad, Ram Katiyar, Santosh K. TI Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE High-fat diet; Malignant progression; Skin tumor; Photocarcinogenesis; Cyclooxygenase-2; Prostaglandins ID NF-KAPPA-B; MOUSE SKIN; INFLAMMATORY RESPONSES; CANCER; INHIBITION; PHOTOCARCINOGENESIS; CYCLOOXYGENASE-2; ACTIVATION; MECHANISMS; EXPRESSION AB Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm(2)) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01-0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression of UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E-2 (P < 0.01), and PGE(2) receptors, and activation of NF-KB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-alpha (P < 0.01), interleukin (IL)-1 beta (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser(473) in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. (C) 2013 Elsevier Inc. All rights reserved. C1 [Vaid, Mudit; Singh, Tripti; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration Merit Review Award [1I01BX001410] FX This work was supported by the funds from the Veterans Administration Merit Review Award (1I01BX001410, S.K.K.). The content of this manuscript does not necessarily represent the official views of the Department of Veterans Administration. We thank Dr. Fiona Hunter for editorial assistance. NR 35 TC 3 Z9 3 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 1 PY 2014 VL 274 IS 1 BP 147 EP 155 DI 10.1016/j.taap.2013.10.030 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 297LD UT WOS:000330256000016 PM 24211275 ER PT S AU Gard, T Holzel, BK Lazar, SW AF Gard, Tim Hoelzel, Britta K. Lazar, Sara W. BE Sequeira, S TI The potential effects of meditation on age-related cognitive decline: a systematic review SO ADVANCES IN MEDITATION RESEARCH: NEUROSCIENCE AND CLINICAL APPLICATIONS SE Annals of the New York Academy of Sciences LA English DT Review CT Conference on Advances in Meditation Research (AMR) - Neuroscience and Clinical Applications CY JAN 17, 2013 CL New York Acad Sci, New York, NY HO New York Acad Sci DE aging; cognitive decline; meditation; mindfulness ID QUALITY-OF-LIFE; STRESS REDUCTION; OLDER-ADULTS; ALZHEIMERS-DISEASE; TRANSCENDENTAL-MEDITATION; CORTICAL PLASTICITY; PHYSICAL-ACTIVITY; PERCEIVED STRESS; DEPRESSION SCALE; CONTROLLED-TRIAL AB With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. C1 [Gard, Tim; Lazar, Sara W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gard, Tim] Univ Giessen, Bender Inst Neuroimaging, D-35390 Giessen, Germany. [Gard, Tim] Maastricht Univ, Fac Psychol & Neurosci, Maastricht, Netherlands. [Hoelzel, Britta K.] Charite, Inst Med Psychol, D-13353 Berlin, Germany. RP Gard, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 120 2nd Ave, Charlestown, MA 02129 USA. EM tgard@nmr.mgh.harvard.edu RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 FU Kusala Foundation, Germany; Kripalu Center for Yoga and Health; Brach Family Charitable Foundation; [R01AT006344]; [R01AT006464] FX There was no dedicated funding for this review. While working on the review, S. W. L. was supported by Grants R01AT006344 and R01AT006464; B. K. H. by the Kusala Foundation, Germany; and T.G. by the Kripalu Center for Yoga and Health, and the Brach Family Charitable Foundation. NR 98 TC 35 Z9 35 U1 9 U2 77 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1307 BP 89 EP 103 DI 10.1111/nyas.12348 PG 15 WC Integrative & Complementary Medicine; Clinical Neurology; Neurosciences SC Integrative & Complementary Medicine; Neurosciences & Neurology GA BJQ51 UT WOS:000329706100010 PM 24571182 ER PT J AU Sczelecki, S Besse-Patin, A Abboud, A Kleiner, S Laznik-Bogoslavski, D Wrann, CD Ruas, JL Haibe-Kains, B Estall, JL AF Sczelecki, Sarah Besse-Patin, Aurele Abboud, Alexandra Kleiner, Sandra Laznik-Bogoslavski, Dina Wrann, Christiane D. Ruas, Jorge L. Haibe-Kains, Benjamin Estall, Jennifer L. TI Loss of Pgc-1 alpha expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE aging; mitochondria; peroxisome proliferator-activated receptor-gamma coactivator-1; muscle; diabetes; inflammation ID CAUSE INSULIN-RESISTANCE; HUMAN SKELETAL-MUSCLE; NF-KAPPA-B; OXIDATIVE-PHOSPHORYLATION; PGC-1 COACTIVATORS; ENERGY-METABOLISM; GENE-EXPRESSION; MITOCHONDRIAL; EXERCISE; MICE AB Diabetes risk increases significantly with age and correlates with lower oxidative capacity in muscle. Decreased expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (Pgc-1 alpha) and target gene pathways involved in mitochondrial oxidative phosphorylation are associated with muscle insulin resistance, but a causative role has not been established. We sought to determine whether a decline in Pgc-1 alpha and oxidative gene expression occurs during aging and potentiates the development of age-associated insulin resistance. Muscle-specific Pgc-1 alpha knockout (MKO) mice and wild-type littermate controls were aged for 2 yr. Genetic signatures of skeletal muscle (microarray and mRNA expression) and metabolic profiles (glucose homeostasis, mitochondrial metabolism, body composition, lipids, and indirect calorimetry) of mice were compared at 3, 12, and 24 mo of age. Microarray and gene set enrichment analysis highlighted decreased function of the electron transport chain as characteristic of both aging muscle and loss of Pgc-1 alpha expression. Despite significant reductions in oxidative gene expression and succinate dehydrogenase activity, young mice lacking Pgc-1 alpha in muscle had lower fasting glucose and insulin. Consistent with loss of oxidative capacity during aging, Pgc-1 alpha and Pgc-1 beta expression were reduced in aged wild-type mouse muscle. Interestingly, the combination of age and loss of muscle Pgc-1 alpha expression impaired glucose tolerance and led to increased fat mass, insulin resistance, and inflammatory markers in white adipose and liver tissues. Therefore, loss of Pgc-1 alpha expression and decreased mitochondrial oxidative capacity contribute to worsening glucose tolerance and chronic systemic inflammation associated with aging. C1 [Sczelecki, Sarah; Besse-Patin, Aurele; Abboud, Alexandra; Estall, Jennifer L.] Inst Rech Clin Montreal, Div Cardiovasc & Metab Dis, Montreal, PQ H2W 1R7, Canada. [Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Div Syst Biol & Med Chem, Montreal, PQ H2W 1R7, Canada. [Sczelecki, Sarah; Estall, Jennifer L.] McGill Univ, Dept Expt Med, Montreal, PQ, Canada. [Besse-Patin, Aurele; Estall, Jennifer L.] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada. [Kleiner, Sandra; Laznik-Bogoslavski, Dina; Wrann, Christiane D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ruas, Jorge L.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Estall, JL (reprint author), IRCM, 110 Ave Des Pins Ouest, Montreal, PQ H2W 1R7, Canada. EM jennifer.estall@ircm.qc.ca RI Haibe-Kains, Benjamin/D-3702-2011; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Ruas, Jorge/0000-0002-1110-2606 FU National Research Council of Canada; Canadian Diabetes Association; Institut de Recherches Cliniques de Montreal FX This research was funded by grants from the National Research Council of Canada (H. L. Holmes Award) and Canadian Diabetes Association to J. L. Estall and the Institut de Recherches Cliniques de Montreal to J. L. Estall and B. Haibe-Kains. NR 56 TC 17 Z9 17 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2014 VL 306 IS 2 BP E157 EP E167 DI 10.1152/ajpendo.00578.2013 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 291VW UT WOS:000329860600004 PM 24280126 ER PT J AU Sierzenski, PR Linton, OW Amis, ES Courtney, DM Larson, PA Mahesh, M Novelline, RA Frush, DP Mettler, FA Timins, JK Tenforde, TS Boice, JD Brink, JA Bushberg, JT Schauer, DA AF Sierzenski, Paul R. Linton, Otha W. Amis, E. Stephen, Jr. Courtney, D. Mark Larson, Paul A. Mahesh, Mahadevappa Novelline, Robert A. Frush, Donald P. Mettler, Fred A. Timins, Julie K. Tenforde, Thomas S. Boice, John D., Jr. Brink, James A. Bushberg, Jerrold T. Schauer, David A. TI Applications of Justification and Optimization in Medical Imaging: Examples of Clinical Guidance for Computed Tomography Use in Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID MINOR HEAD-INJURY; DECISION-SUPPORT; UNITED-STATES; CRITICAL-ISSUES; CT; TRAUMA; POLICY; RULE; PERFORMANCE; MANAGEMENT AB Availability, reliability, and technical improvements have led to continued expansion of computed tomography (CT) imaging. During a CT scan, there is substantially more exposure to ionizing radiation than with conventional radiography. This has led to questions and critical conclusions about whether the continuous growth of CT scans should be subjected to review and potentially restraints or, at a minimum, closer investigation. This is particularly pertinent to populations in emergency departments, such as children and patients who receive repeated CT scans for benign diagnoses. During the last several decades, among national medical specialty organizations, the American College of Emergency Physicians and the American College of Radiology have each formed membership working groups to consider value, access, and expedience and to promote broad acceptance of CT protocols and procedures within their disciplines. Those efforts have had positive effects on the use criteria for CT by other physician groups, health insurance carriers, regulators, and legislators. C1 [Sierzenski, Paul R.] Christiana Care Hlth Syst, Dept Emergency Med, Sect Emergency Ultrasound, Newark, DE USA. [Amis, E. Stephen, Jr.] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. [Amis, E. Stephen, Jr.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Courtney, D. Mark] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Larson, Paul A.] Radiol Associates Fox Valley, Neenah, WI USA. [Mahesh, Mahadevappa] Johns Hopkins Univ, Sch Med, Russel H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Novelline, Robert A.] Harvard Univ, Sch Med, Boston, MA USA. [Novelline, Robert A.] Massachusetts Gen Hosp, Emergency Radiol Div, Boston, MA 02114 USA. [Frush, Donald P.] Duke Univ, Med Ctr, Div Pediat Radiol, Durham, NC USA. [Mettler, Fred A.] New Mexico VAHCS, Dept Radiol, Albuquerque, NM USA. [Linton, Otha W.; Tenforde, Thomas S.; Boice, John D., Jr.; Schauer, David A.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA. [Brink, James A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bushberg, Jerrold T.] Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. RP Sierzenski, PR (reprint author), Christiana Care Hlth Syst, Dept Emergency Med, Sect Emergency Ultrasound, Newark, DE USA. EM psierzenski@christianacare.org RI Frush, Donald/M-6457-2015 OI Frush, Donald/0000-0002-6928-4465 NR 50 TC 9 Z9 10 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 2014 VL 63 IS 1 BP 25 EP 32 DI 10.1016/j.annemergmed.2013.08.027 PG 8 WC Emergency Medicine SC Emergency Medicine GA 292GN UT WOS:000329890300007 PM 24134958 ER PT J AU Baumgartner, WA Mathisen, DJ AF Baumgartner, William A. Mathisen, Douglas J. TI The STS Annual Meeting SO ANNALS OF THORACIC SURGERY LA English DT Article C1 [Baumgartner, William A.] Johns Hopkins Univ Hosp, Div Cardiac Surg, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Baumgartner, WA (reprint author), Johns Hopkins Univ Hosp, Div Cardiac Surg, 600 N Wolfe St,Blalock 618, Baltimore, MD 21287 USA. EM wbaumgar@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2014 VL 97 IS 1 SU S BP S9 EP S15 DI 10.1016/j.athoracsur.2013.10.014 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 290KB UT WOS:000329753500004 PM 24384254 ER PT J AU Grover, FL Shahian, DM Clark, RE Edwards, FH AF Grover, Frederick L. Shahian, David M. Clark, Richard E. Edwards, Fred H. TI The STS National Database SO ANNALS OF THORACIC SURGERY LA English DT Article ID ADULT CARDIAC-SURGERY; BYPASS-GRAFTING SURGERY; THORACIC-SURGEONS; RISK MODELS; QUALITY MEASUREMENT; OPERATIVE MORTALITY; SOCIETY; PREDICTORS; MORBIDITY; COSTS C1 [Grover, Frederick L.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO 80045 USA. Vet AffairsMed Ctr, Denver Dept, Denver, CO USA. Massachusetts Gen Hosp, Ctr Qual & Safety, Dept Surg, Sudbury, MA USA. Massachusetts Gen Hosp, Ctr Qual & Safety, Dept Surg, Sewickley, PA USA. Univ Florida, Jacksonville, FL USA. RP Grover, FL (reprint author), Univ Colorado, Sch Med, Dept Surg, Anschutz Med Campus,Acad Off 1,Bldg L15,Room 6613, Aurora, CO 80045 USA. EM frederick.grover@ucdenver.edu NR 32 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2014 VL 97 IS 1 SU S BP S48 EP S54 DI 10.1016/j.athoracsur.2013.10.015 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 290KB UT WOS:000329753500012 PM 24384250 ER PT J AU Minces, LR Nguyen, MH Mitsani, D Shields, RK Kwak, EJ Silveira, FP Abdel-Massih, R Pilewski, JM Crespo, MM Bermudez, C Bhama, JK Toyoda, Y Clancy, CJ AF Minces, Lucio R. Hong Nguyen, M. Mitsani, Dimitra Shields, Ryan K. Kwak, Eun J. Silveira, Fernanda P. Abdel-Massih, Rima Pilewski, Joseph M. Crespo, Maria M. Bermudez, Christian Bhama, Jay K. Toyoda, Yoshiya Clancy, Cornelius J. TI Ganciclovir-Resistant Cytomegalovirus Infections among Lung Transplant Recipients Are Associated with Poor Outcomes despite Treatment with Foscarnet-Containing Regimens SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID VALGANCICLOVIR PROPHYLAXIS; INTRAVENOUS GANCICLOVIR; PREVENT CYTOMEGALOVIRUS; DRUG-RESISTANCE; IMMUNE GLOBULIN; CMV INFECTION; SINGLE-CENTER; DISEASE; EMERGENCE; EXPERIENCE AB Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for >= 6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log(10) copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity. C1 [Minces, Lucio R.; Hong Nguyen, M.; Mitsani, Dimitra; Shields, Ryan K.; Kwak, Eun J.; Silveira, Fernanda P.; Abdel-Massih, Rima; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA. [Pilewski, Joseph M.; Crespo, Maria M.] Univ Pittsburgh, Dept Med, Dept Pulm Med, Pittsburgh, PA USA. [Bermudez, Christian; Bhama, Jay K.; Toyoda, Yoshiya] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA. EM mhn5@pitt.edu NR 44 TC 12 Z9 12 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2014 VL 58 IS 1 BP 128 EP 135 DI 10.1128/AAC.00561-13 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 287ZL UT WOS:000329581100016 PM 24145525 ER PT J AU Wiederhold, NP Pennick, GJ Dorsey, SA Furmaga, W Lewis, JS Patterson, TF Sutton, DA Fothergill, AW AF Wiederhold, Nathan P. Pennick, Gennethel J. Dorsey, Sheryl A. Furmaga, Wieslaw Lewis, James S., II Patterson, Thomas F. Sutton, Deanna A. Fothergill, Annette W. TI A Reference Laboratory Experience of Clinically Achievable Voriconazole, Posaconazole, and Itraconazole Concentrations within the Bloodstream and Cerebral Spinal Fluid SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; CELL TRANSPLANT RECIPIENTS; VERSUS-HOST-DISEASE; PULMONARY ASPERGILLOSIS; ANTIFUNGAL PROPHYLAXIS; NEUTROPENIC PATIENTS; CONTROLLED-TRIAL; EXPOSURE-RESPONSE; ADVERSE EVENTS; MURINE MODEL AB Interest in antifungal therapeutic-drug monitoring has increased due to studies demonstrating associations between concentrations and outcomes. We reviewed the antifungal drug concentration database at our institution to gain a better understanding of achievable triazole drug levels. Antifungal concentrations were measured by high-performance liquid chromatography (HPLC), ultraperformance liquid chromatography and single-quadrupole mass spectrometry (UPLC/MS), or a bioassay. For this study, only confirmed human bloodstream (serum or plasma) and cerebral spinal fluid (CSF) concentrations of voriconazole, posaconazole, and itraconazole were analyzed. The largest numbers of bloodstream and CSF samples were found for voriconazole (14,370 and 173, respectively). Voriconazole bloodstream concentrations within the range of 1 to 5.5 mu g/ml represented 50.6% of samples. Levels below the lower limit of quantification (0.2 mu g/ml) were observed in 14.6% of samples, and 10.4% of samples had levels of >= 5.5 mu g/ml. CSF voriconazole levels ranged from undetectable to 15.3 mu g/ml and were <0.2 mu g/ml in 11% of samples. Posaconazole bloodstream concentrations were >= 0.7 and >= 1.25 mu g/ml in 41.6% and 18.9% of samples, respectively. Posaconazole was detected in only 4 of 22 CSF samples (undetectable to 0.56 mu g/ml). Itraconazole levels, as measured by UPLC/MS, were >= 0.5 mu g/ml in 43.3% and were undetectable in 33.9% of bloodstream samples. In contrast, when measured by a bioassay, itraconazole/hydroxyitraconazole bloodstream concentrations were >= 1.0 mu g/ml in 72.9% of samples and were undetectable in 18% of samples. These results indicate that there is marked variability in bloodstream concentrations achieved with these three azoles. In addition, many levels within the bloodstream for each azole and for voriconazole and posaconazole in the CSF were undetectable or below thresholds associated with efficacy. C1 [Wiederhold, Nathan P.; Pennick, Gennethel J.; Dorsey, Sheryl A.; Furmaga, Wieslaw; Lewis, James S., II; Patterson, Thomas F.; Sutton, Deanna A.; Fothergill, Annette W.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lewis, James S., II] Univ Hlth Syst, San Antonio, TX USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Merck; Astellas; bioMerieux; Viamet; Medicis; Merz; F2G FX N.P.W. has received research support from Merck, Astellas, bioMerieux, Viamet, Medicis, Merz, and F2G and has served on advisory boards for Merck, Astellas, Toyama, and Viamet. NR 57 TC 15 Z9 16 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2014 VL 58 IS 1 BP 424 EP 431 DI 10.1128/AAC.01558-13 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 287ZL UT WOS:000329581100054 PM 24189246 ER PT J AU Widge, AS Avery, DH Zarkowski, P AF Widge, Alik S. Avery, David H. Zarkowski, Paul TI Methodology and the Limits of QEEG: Reply to Olbrich & Arns SO BRAIN STIMULATION LA English DT Letter ID EEG C1 [Widge, Alik S.; Avery, David H.; Zarkowski, Paul] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Widge, AS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, 149 13th St,Room 2612, Charlestown, MA 02129 USA. EM awidge@partners.org NR 7 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2014 VL 7 IS 1 BP 148 EP 149 DI 10.1016/j.brs.2013.09.008 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 293BV UT WOS:000329947300025 PM 24252322 ER PT J AU Luoh, SW Ramsey, B Park, B Keenan, E AF Luoh, Shiuh-Wen Ramsey, Betsy Park, Byung Keenan, Edward TI Quantitative Progesterone Receptor Expression and Efficacy of Anti-estrogen Therapy in Breast Cancer SO BREAST JOURNAL LA English DT Article DE anti-estrogen therapy; predictive marker; progesterone receptor ID ADJUVANT ENDOCRINE THERAPY; LIGAND-BINDING ASSAY; ESTROGEN-RECEPTOR; PREDICTING RESPONSE; IMMUNOHISTOCHEMISTRY; TAMOXIFEN; HER2; IMPROVES; ER AB The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti-estrogen therapies is well-established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti-estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme-linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan-Meier actuarial survival analysis and the log-rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti-estrogen treated patients, when the ER and PR positivity cut-off was set at 1.0fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR- tumors for both breast cancer-free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti-estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti-estrogen therapy in breast cancer patients. C1 [Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR USA. [Luoh, Shiuh-Wen; Ramsey, Betsy; Park, Byung; Keenan, Edward] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Knight Canc Inst, Portland, OR 97201 USA. [Ramsey, Betsy; Keenan, Edward] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Park, Byung] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Luoh, SW (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, 3181 SW Sam,Jackson Pk Rd,MC L586, Portland, OR 97239 USA. EM luohs@ohsu.edu NR 24 TC 3 Z9 3 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD JAN PY 2014 VL 20 IS 1 BP 46 EP 52 DI 10.1111/tbj.12200 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 291EQ UT WOS:000329810900008 PM 24261828 ER PT J AU Betancourt, JR Corbett, J Bondaryk, MR AF Betancourt, Joseph R. Corbett, James Bondaryk, Matthew R. TI Addressing Disparities and Achieving Equity Cultural Competence, Ethics, and Health-care Transformation SO CHEST LA English DT Article ID RACIAL/ETHNIC DISPARITIES; HEART-FAILURE; HOSPITALS; EDUCATION; QUALITY; SAFETY; SYSTEM; RACE AB The passage of health-care reform and current efforts in payment reform signal the beginning of a significant transformation of the US health-care system. An entire new set of structures is being developed to facilitate increased access to care that is cost-effective and of high quality. As described in The Institute of Medicine report "Crossing the Quality Chasm," our nation is charting a path toward quality health care that aims to be safe, efficient, effective, timely, patient-centered, and equitable. As our health-care system rapidly undergoes dramatic transformation, several truths-and challenges-remain. First, racial and ethnic disparities in health care persist and are a clear sign of inequality in quality. Second, although the root causes for these disparities are complex, there exists a well-developed set of evidence-based approaches to address them; among these is improving the cultural competence of health-care providers and the health-care system. Third, as part of our care redesign, we must assure that we are prepared to meet the ethical challenges ahead and reassert the importance of equity, fairness, and caring as key building blocks of a new care delivery system. As we move ahead, it is critical to assure that our health-care system is culturally competent and has the capacity to deliver high-quality care for all, while eliminating disparities and assuring equity. Disparities are unjust, unethical, costly, and unacceptable-and integrating strategies to achieve equity as part of our health-care system's transformation will give us an incredible opportunity to comprehensively address them. C1 [Betancourt, Joseph R.; Bondaryk, Matthew R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Betancourt, Joseph R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Corbett, James] Community Hlth & Eth Steward Hlth Care, Boston, MA USA. RP Betancourt, JR (reprint author), 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM jbetancourt@partners.org NR 40 TC 14 Z9 14 U1 3 U2 22 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2014 VL 145 IS 1 BP 143 EP 148 DI 10.1378/chest.13-0634 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 293JD UT WOS:000329966300030 PM 24394825 ER PT J AU Kangovi, S Grande, D AF Kangovi, Shreya Grande, David TI Transitional Care Management Reimbursement to Reduce COPD Readmission SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; NATIONAL DEMONSTRATION PROJECT; PATIENT SAFETY STRATEGY; FOLLOW-UP; SOCIOECONOMIC-STATUS; HOSPITAL DISCHARGE; MEDICAL HOME; AMBULATORY-CARE; HEART-FAILURE AB Reducing preventable readmissions for COPD is an important national health policy goal. Thus far, Centers for Medicare & Medicaid Services (CMS) policies focused on incentivizing improvements in inpatient quality have had variable success. In its 2013 physician-payment rule, CMS announced new payments that reimburse ambulatory care providers for timely posthospital visits and transitional care management services. CMS hopes that posthospital transitional care and services will substitute for readmission, but the evidence supporting this hypothesis is mixed. In this article, we discuss ways for ambulatory pulmonologists to leverage transitional care management payments to enhance access for their patients with COPD while minimizing the risk of a paradoxic increase in readmission rates. C1 [Kangovi, Shreya] Univ Penn, Philadelphia Vet Affairs Med Ctr, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Grande, David] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Kangovi, S (reprint author), 13th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kangovi@mail.med.upenn.edu NR 59 TC 3 Z9 3 U1 3 U2 14 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2014 VL 145 IS 1 BP 149 EP 155 DI 10.1378/chest.13-0787 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 293JD UT WOS:000329966300031 PM 24394826 ER PT J AU Bastawrous, S Hirschmann, JV AF Bastawrous, Sarah Hirschmann, Jan V. TI A Man in His Early 70s With Progressive Dyspnea and Abnormal Fundoscopic Examination SO CHEST LA English DT Editorial Material ID DRUG-ABUSERS; TALCOSIS C1 [Bastawrous, Sarah] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA. [Hirschmann, Jan V.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Bastawrous, Sarah] Univ Washington, Dept Radiol, UW Med, Seattle, WA 98195 USA. [Hirschmann, Jan V.] Univ Washington, Dept Med, UW Med, Seattle, WA USA. RP Bastawrous, S (reprint author), VA Puget Sound Hlth Care Syst, Dept Radiol, Mail Box 358280,S-114,1660 S Columbian Way, Seattle, WA 98108 USA. EM ssheikh@u.washington.edu OI Bastawrous, Sarah/0000-0002-7690-3121 NR 7 TC 1 Z9 1 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2014 VL 145 IS 1 BP 178 EP 181 DI 10.1378/chest.13-1277 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 293JD UT WOS:000329966300036 PM 24394831 ER PT J AU Yeh, DD Foster, E AF Yeh, Doreen DeFaria Foster, Elyse TI Is MRI the Preferred Method for Evaluating Right Ventricular Size and Function in Patients With Congenital Heart Disease? MRI Is Not the Preferred Method for Evaluating Right Ventricular Size and Function in Patients With Congenital Heart Disease SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article ID CARDIAC MAGNETIC-RESONANCE; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; SYSTEMIC RIGHT VENTRICLE; GREAT-ARTERIES; LONGITUDINAL STRAIN; REPAIRED TETRALOGY; EJECTION FRACTION; SYSTOLIC FUNCTION; ADULT PATIENTS; COMPUTED-TOMOGRAPHY C1 [Yeh, Doreen DeFaria] Massachusetts Gen Hosp, Div Cardiol, Adult Congenital Heart Dis Program, Echocardiog Sect, Boston, MA 02114 USA. [Foster, Elyse] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Foster, E (reprint author), Univ Calif San Francisco, Div Cardiol, Med Ctr, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM foster@medicine.ucsf.edu FU Abbott Vascular FX Dr DeFariaYeh reports no disclosures. Dr Foster discloses grant support from Abbott Vascular. NR 48 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2014 VL 7 IS 1 BP 198 EP 205 DI 10.1161/CIRCIMAGING.113.000395 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 293BF UT WOS:000329945700026 ER PT J AU Felgentreff, K Siepe, M Kotthoff, S von Kodolitsch, Y Schachtrup, K Notarangelo, LD Walter, JE Ehl, S AF Felgentreff, Kerstin Siepe, Matthias Kotthoff, Stefan von Kodolitsch, Yskert Schachtrup, Kristina Notarangelo, Luigi D. Walter, Jolan E. Ehl, Stephan TI Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - Contribution to new findings of immune dysregulation in connective tissue disorders SO CLINICAL IMMUNOLOGY LA English DT Article DE TGF-beta; Loeys-Dietz syndrome; Hyper-IgE; Eczema; Allergy ID GROWTH-FACTOR-BETA; TGF-BETA; MARFAN-SYNDROME; AORTIC-ANEURYSM; MOUSE MODEL; T-CELLS; MUTATIONS; RECEPTOR; STAT3; ACTIVATION AB Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming growth factor beta (TGF beta) receptor. Affected patients are identified by vascular aneurysms with tortuosity and distinct morphological presentations similar to Marfan syndrome; however, an additional predisposition towards asthma and allergy has recently been found. We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild allergic manifestations with normal up to moderately increased IgE were observed in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES patients illustrates the significant overlap of both syndromes including eczema and elevated IgE as well as skeletal and connective tissue manifestations. (C) 2013 Elsevier Inc. All rights reserved. C1 [Felgentreff, Kerstin; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA USA. [Felgentreff, Kerstin; Schachtrup, Kristina; Ehl, Stephan] Univ Hosp Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Siepe, Matthias] Univ Heart Ctr Freiburg Bad Krozingen, Freiburg, Germany. [Kotthoff, Stefan] Univ Hosp Munster, Dept Pediat Cardiol, Munster, Germany. [von Kodolitsch, Yskert] Univ Heart Ctr Hamburg Eppendorf, Hamburg, Germany. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. [Walter, Jolan E.] Massachusetts Gen Hosp, Div Allergy & Immunol, Boston, MA 02114 USA. [Felgentreff, Kerstin; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. RP Felgentreff, K (reprint author), Boston Childrens Hosp, Div Immunol, Karp Bldg 10th Floor,1 Blackfan Circle, Boston, MA 02115 USA. EM kerstin.felgentreff@childrens.harvard.edu; stephan.ehl@uniklinik-freiburg.de RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Schachtrup, Kristina/0000-0002-9385-8254; Ehl, Stephan/0000-0002-9265-2721 FU German Federal Ministry of Education and Research [BMBF 01 EO 0803]; German Research Foundation [FE 1253/1-1]; Manton Foundation, USA FX This work was supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0803), the German Research Foundation (FE 1253/1-1), and The Manton Foundation, USA. NR 34 TC 8 Z9 8 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2014 VL 150 IS 1 BP 43 EP 50 DI 10.1016/j.clim.2013.11.008 PG 8 WC Immunology SC Immunology GA 295AF UT WOS:000330088300005 PM 24333532 ER PT J AU Ritholz, MD Wolpert, H Beste, M Atakov-Castillo, A Luff, D Garvey, KC AF Ritholz, Marilyn D. Wolpert, Howard Beste, Meg Atakov-Castillo, Astrid Luff, Donna Garvey, Katharine C. TI Patient-Provider Relationships Across the Transition From Pediatric to Adult Diabetes Care A Qualitative Study SO DIABETES EDUCATOR LA English DT Article ID HEALTH-CARE; YOUNG-ADULTS; GLYCEMIC CONTROL; CHRONIC DISEASE; SERVICES; ADOLESCENTS; EXPERIENCES; PEOPLE; RECOMMENDATIONS; OUTCOMES AB Purpose The purpose of this study was to explore perceptions that emerging adults with type 1 diabetes (T1D) have of their patient-provider relationships across the transition from pediatric to adult care. Methods Twenty-six emerging adults with T1D (mean age 26.2 2.5 years) participated in 5 focus groups stratified by current level of glycemic control (A1C). Coded audio-recorded data were analyzed using thematic analysis and aided by NVivo software. Results Three major themes emerged from the analysis: (1) loss and gain in provider relationships across the transitionpatients expressed 3 key responses to leaving pediatric providers that differed by A1C levels: sad reluctance and natural progression (mean A1C +/- SD 7.4% +/- 0.6%) and wanting to go (mean A1C +/- SD 9.8% +/- 1.0%); (2) partners in care versus on one's ownpatients valued how adult providers' collaborative conversations promoted their involvement and accountability compared to parent-centric interactions with pediatric providers, but they also expressed ambivalence over increased independence in adult care; (3) improving provider approaches to transitionpatients recommended that pediatric providers actively promote emerging adults' autonomy while maintaining parental support, communication with adult providers, and follow-up with transitioning patients. Conclusions Findings highlight the importance of enhanced provider awareness of T1D emerging adults' complex feelings about the transition in care. Improved integration of individual- and family-centered approaches to developmentally tailored diabetes care is needed to augment patient and provider relationships. C1 [Ritholz, Marilyn D.; Wolpert, Howard; Beste, Meg; Atakov-Castillo, Astrid] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, Marilyn D.; Luff, Donna; Garvey, Katharine C.] Boston Childrens Hosp, Boston, MA USA. [Ritholz, Marilyn D.; Wolpert, Howard; Luff, Donna; Garvey, Katharine C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ritholz, MD (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM marilyn.ritholz@joslin.harvard.edu FU Agency for Healthcare Research and Quality [T32-HS000063]; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007699-30]; William Randolph Hearst Foundation FX Dr Garvey was supported by the Agency for Healthcare Research and Quality (T32-HS000063), the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007699-30), and the William Randolph Hearst Foundation. NR 46 TC 10 Z9 10 U1 3 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 EI 1554-6063 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN PY 2014 VL 40 IS 1 BP 40 EP 47 DI 10.1177/0145721713513177 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 291YU UT WOS:000329869600002 PM 24258251 ER PT J AU Berg, AT Loddenkemper, T Baca, CB AF Berg, Anne T. Loddenkemper, Tobias Baca, Christine B. TI Diagnostic delays in children with early onset epilepsy: Impact, reasons, and opportunities to improve care SO EPILEPSIA LA English DT Article DE Health services; Barriers to care; Pediatrics; Development ID ADAPTIVE-BEHAVIOR; SEIZURE; EEG; SURGERY; TIME; OUTCOMES; INFANCY; ACCESS; AGE AB PurposeDelayed diagnosis of early onset epilepsy is a potentially important and avoidable complication in epilepsy care. We examined the frequency of diagnostic delays in young children with newly presenting epilepsy, their developmental impact, and reasons for delays. MethodsChildren who developed epilepsy before their third birthday were identified in a prospective community-based cohort. An interval 1month from second seizure to diagnosis was considered a delay. Testing of development at baseline and for up to 3years after and of intelligence quotient (IQ) 8-9years later was performed. Detailed parental baseline interview accounts and medical records were reviewed to identify potential reasons for delays. Factors associated with delays included the parent, child, pediatrician, neurologist, and scheduling. ResultsDiagnostic delays occurred in 70 (41%) of 172 children. Delays occurred less often if children had received medical attention for the first seizure (p<0.0001), previously had neonatal or febrile seizures (p=0.02), had only convulsions before diagnosis (p=0.005), or had a college-educated parent (p=0.01). A 1month diagnostic delay was associated with an average 7.4 point drop (p=0.02) in the Vineland Scales of Adaptive Behavior motor score. The effect was present at diagnosis, persisted for at least 3years, and was also apparent in IQ scores 8-9years later, which were lower in association with a diagnostic delay by 8.4 points (p=0.06) for processing speed up to 14.5 points (p=0.004) for full scale IQ, after adjustment for parental education and other epilepsy-related clinical factors. Factors associated with delayed diagnosis included parents not recognizing events as seizures (N=47), pediatricians missing or deferring diagnosis (N=15), neurologists deferring diagnosis (N=7), and scheduling problems (N=11). SignificanceDiagnostic delays occur in many young children with epilepsy. They are associated with substantial decrements in development and IQ later in childhood. Several factors influence diagnostic delays and may represent opportunities for intervention and improved care. C1 [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat, Epilepsy Ctr, Chicago, IL USA. [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Northwestern Mem Feinberg Sch Med, Chicago, IL USA. [Loddenkemper, Tobias] Harvard Univ, Sch Med, Div Epilepsy & Clin Neurophysiol, Dept Neurol,Boston Childrens Hosp, Boston, MA 02115 USA. [Baca, Christine B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Baca, Christine B.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. RP Berg, AT (reprint author), Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, 225 East Chicago Ave,Box 29, Chicago, IL 60611 USA. EM atberg@luriechildrens.org FU National Institute of Neurological Disorders and Stroke [R37-NS31146] FX This study was funded by a grant from the National Institute of Neurological Disorders and Stroke R37-NS31146. NR 38 TC 7 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JAN PY 2014 VL 55 IS 1 BP 123 EP 132 DI 10.1111/epi.12479 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 292HX UT WOS:000329893900016 PM 24313635 ER PT J AU Chen, DK Maheshwari, A Franks, R Trolley, GC Robinson, JS Hrachovy, RA AF Chen, David K. Maheshwari, Atul Franks, Romay Trolley, Gregory C. Robinson, Jordan S. Hrachovy, Richard A. TI Brief group psychoeducation for psychogenic nonepileptic seizures: A neurologist-initiated program in an epilepsy center SO EPILEPSIA LA English DT Article DE Psychogenic nonepileptic seizures; Psychotherapy; Psychoeducation; Work and Social Adjustment Scale; Psychosocial functioning ID SOCIAL-ADJUSTMENT SCALE; QUALITY-OF-LIFE; DIAGNOSIS; PSEUDOSEIZURE; DISORDERS; WORK; COMMUNICATION; COMORBIDITY; PERSONALITY; RELIABILITY AB ObjectiveTo evaluate therapeutic efficacy upon augmenting the initial communication to patients regarding the diagnosis of psychogenic nonepileptic seizures (PNES) with a novel, brief group psychoeducation administered by the same team that provided the video-electroencephalography (VEEG) confirmed diagnosis and within 4weeks of the diagnosis. MethodsPrior to discharge from the epilepsy monitoring unit (EMU), a standardized communication strategy was utilized to explain the diagnosis of PNES to all patients prior to enrollment. Enrolled patients were then randomized to either participation in three successive and monthly group psychoeducational sessions (intervention group), or routine seizure clinic follow-up visits (control group). Both groups completed questionnaires at time of enrollment, and then at approximately 3months (follow-up 1) and 6months (follow-up 2) after discharge, assessing for: (1) primary outcomes that include a measure of psychosocial functioning, as well as interval difference in seizure frequency/intensity; and (2) secondary outcomes that include interval seizure-related emergency room visits or hospitalizations, development of new and medically unexplained symptoms, and results of an internal measure of knowledge and perception outcomes. ResultsThe majority (73%) of patients from the intervention group commenced on therapy sessions within 4weeks after learning of the diagnosis. Although we did not observe significant group difference in seizure frequency/intensity, patients from the intervention group showed significant improvement on the Work and Social Adjustment Scale (WSAS) scores at both follow-up 1 (p=0.013) and follow-up 2 (p=0.038) after discharge from the EMU. In addition, we observed a trend toward lesser likelihood for seizure-related emergency room visits or hospitalizations for the intervention group (p=0.184), as well as meaningful insights from an internal measure of intervention outcomes. SignificanceThese findings suggest that our cost/resource effective, brief group psychoeducational program, when administered early and by the same team who confirmed and communicated the diagnosis of PNES, may contribute to significant functional improvement among participating patients. C1 [Chen, David K.; Maheshwari, Atul; Hrachovy, Richard A.] Baylor Coll Med, Dept Neurol, Peter Kellaway Sect Neurophysiol, Houston, TX 77030 USA. [Chen, David K.; Franks, Romay; Hrachovy, Richard A.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Trolley, Gregory C.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Robinson, Jordan S.] Baylor Coll Med, Dept Psychol & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Chen, DK (reprint author), MEDVAMC, 2002 Holcombe Blvd,NCL 127, Houston, TX 77030 USA. EM dkchen@bcm.edu FU Department of Veteran Affairs, Epilepsy Centers of Excellence (ECoE) FX The authors are grateful to the staff and patients of the epilepsy monitoring unit at Michael E. DeBakey VA Medical Center for their involvement in this study. This research is based on work supported in part by the Department of Veteran Affairs, Epilepsy Centers of Excellence (ECoE). NR 40 TC 18 Z9 18 U1 4 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JAN PY 2014 VL 55 IS 1 BP 156 EP 166 DI 10.1111/epi.12481 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 292HX UT WOS:000329893900020 PM 24446955 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Pathophysiology of Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 4 TC 0 Z9 0 U1 2 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 10 EP 16 PG 7 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000002 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Research in Neuroprotection, Regeneration, and Repair of the Injured Spinal Cord SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID CLINICAL-TRIALS; THERAPIES C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 17 EP 22 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000003 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Epidemiology of Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 23 EP 29 PG 7 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000004 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Primary Prevention of Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 30 EP 34 PG 5 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000005 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Prehospital Management of Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 35 EP 40 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000006 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Imaging of the Injured Spine and Spinal Cord SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 41 EP 52 PG 12 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000007 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Early Hospital Care Following SCI: Medical, Surgical, and Rehabilitation SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; MANAGEMENT C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 53 EP 65 PG 13 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000008 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Spinal Orthoses SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID MANAGEMENT C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 66 EP 70 PG 5 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000009 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Neurological Assessment for Classification of Traumatic Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 71 EP 85 PG 15 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000010 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Traumatic Spinal Cord Injury in Children SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 86 EP 93 PG 8 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000011 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Nontraumatic Myelopathies: Overview and Approach SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 94 EP 98 PG 5 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000012 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Cervical Spondylotic Myelopathy SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 99 EP 106 PG 8 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000013 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Nontraumatic Cauda Equina Syndrome SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 107 EP 111 PG 5 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000014 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Tumors of the Spine and Spinal Cord SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID METASTATIC PARAPLEGIA; REHABILITATION; PERSPECTIVES; LIMITATIONS; MANAGEMENT C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 112 EP 115 PG 4 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000015 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Vascular Myelopathy-Spinal Cord Infarction SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 116 EP 119 PG 4 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000016 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Spinal Cord Hemorrhage and Spinal Arteriovenous Malformations SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID VASCULAR MALFORMATIONS; MANAGEMENT C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 120 EP 123 PG 4 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000017 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Multiple Sclerosis SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID MULTIMODAL APPROACH; SYMPTOMS; MANAGEMENT; MOBILITY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 124 EP 139 PG 16 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000018 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Spinal Arachnoiditis SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 140 EP 141 PG 2 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000019 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Infections of the Spine and Spinal Cord SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 142 EP 145 PG 4 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000020 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Nutritional, Toxic, and Environmental Myelopathies SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 146 EP 151 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000021 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Spina Bifida/Myelomeningocele SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID BIFIDA; CHILDREN C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 152 EP 157 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000022 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Chiari Malformation and Developmental Syringomyelia SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 158 EP 161 PG 4 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000023 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Hereditary Spastic Paraplegia SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 162 EP 166 PG 5 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000024 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Amyotrophic Lateral Sclerosis/Adult Motor Neuron Disease SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID DIAGNOSIS C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 167 EP 182 PG 16 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000025 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Functional Outcomes Following SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; MOTOR RECOVERY; AMBULATION C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 183 EP 195 PG 13 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000026 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Physical Rehabilitation Activities and Therapeutic Interventions in SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 196 EP 201 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000027 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Upper Extremity Function in Tetraplegia SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 202 EP 211 PG 10 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000028 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Wheelchair Prescription and Wheelchair Mobility After SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; TECHNOLOGY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 212 EP 220 PG 9 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000029 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Walking After Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 221 EP 228 PG 8 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000030 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Medical Complications and Consequences of SCI: Overview SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 229 EP 231 PG 3 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000031 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Respiratory Issues in Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SLEEP C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 232 EP 251 PG 20 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000032 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Cardiovascular and Autonomic Consequences: Overview SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; NEUROGENIC ORTHOSTATIC HYPOTENSION; MANAGEMENT; THERMOREGULATION; THROMBOEMBOLISM; COMPLICATIONS; INDIVIDUALS; DYSREFLEXIA; EXERCISE C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 252 EP 282 PG 31 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000033 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Genitourinary Consequences: Overview SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; URINARY-TRACT-INFECTIONS; UROLITHIASIS; INDIVIDUALS; PREVENTION; MANAGEMENT; ACCURACY; RISK C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 283 EP 303 PG 21 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000034 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Sexual Function and Reproductive Health After SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; DYSFUNCTION; MEN C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 8 TC 0 Z9 0 U1 1 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 304 EP 312 PG 9 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000035 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Gastrointestinal Consequences: Overview SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; DYSPHAGIA C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 313 EP 327 PG 15 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000036 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Pressure Ulcers SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 328 EP 340 PG 13 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000037 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Neurological and Musculoskeletal Consequences: Overview SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; TRAUMATIC BRAIN-INJURY; BASIC DATA SET; HETEROTOPIC OSSIFICATION; PAIN; MANAGEMENT; SPASTICITY; ETIOLOGY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 341 EP 371 PG 31 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000038 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Metabolic and Endocrine Issues: Overview SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; BONE LOSS; OSTEOPOROSIS; MANAGEMENT; EXERCISE; MASS C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 19 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 372 EP 386 PG 15 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000039 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Aging With a Spinal Cord Injury SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 387 EP 393 PG 7 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000040 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Psychological Considerations Following SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; PSYCHOSOCIAL ISSUES C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 394 EP 404 PG 11 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000041 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Socioeconomic Consequences and Quality of Life SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; MEDICINE C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 405 EP 412 PG 8 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000042 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Exercise and Sports After SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 413 EP 418 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000043 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Employment After SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID INJURY C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 419 EP 425 PG 7 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000044 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Driving and Transportation Access After SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID MULTIPLE-SCLEROSIS C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 426 EP 430 PG 5 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000045 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Systems of Care for SCI SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; HEALTH EVALUATION; VETERANS C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 431 EP 436 PG 6 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000046 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Patient Safety in SCI Care SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; STRATEGY; REHABILITATION C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 437 EP 443 PG 7 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000047 ER PT B AU Sabharwal, S AF Sabharwal, Sunil BA Sabharwal, S BF Sabharwal, S TI Ethical Issues in SCI Practice SO ESSENTIALS OF SPINAL CORD MEDICINE LA English DT Article; Book Chapter ID SPINAL-CORD-INJURY; GUIDELINES C1 [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. [Sabharwal, Sunil] Harvard Univ, Sch Med, Boston, MA USA. RP Sabharwal, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury, Boston, MA USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-38-3 PY 2014 BP 444 EP 452 PG 9 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BJL41 UT WOS:000328866000048 ER PT J AU Brahmer, JR Lee, JW Traynor, AM Hidalgo, MM Kolesar, JM Siegfried, JM Guaglianone, PP Patel, JD Keppen, MD Schiller, JH AF Brahmer, J. R. Lee, J. W. Traynor, A. M. Hidalgo, M. M. Kolesar, J. M. Siegfried, J. M. Guaglianone, P. P. Patel, J. D. Keppen, M. D. Schiller, J. H. TI Dosing to rash: A phase II trial of the first-line erlotinib for patients with advanced non-small-cell lung cancer an Eastern Cooperative Oncology Group Study (E3503) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Erlotinib; Phase II; NSCLC ID GEFITINIB; ADENOCARCINOMA; CHEMOTHERAPY; PREDICTORS; MUTATIONS; SURVIVAL; THERAPY AB Background: The development of a rash has been retrospectively associated with increased response and improved survival when treated with erlotinib at the standard dose of 150 mg per day. The objective of this trial was to evaluate the association of the activity of erlotinib in the first-line setting in patients with advanced non-small-cell lung cancer (NSCLC) with the development of a tolerable rash via dose escalation of erlotinib or tumour characteristics. Methods: Patients, with advanced NSCLC without prior systemic therapy, were treated with erlotinib 150 mg orally per day. The dose was increased by 25 mg every two weeks until the development of grade 2/tolerable rash or other dose limiting toxicity. Tumour biopsy specimens were required for inclusion. Results: The study enrolled 137 patients, 135 were evaluable for safety and 124 were eligible and evaluable for response. Only 73 tumour samples were available for analysis. Erlotinib dose escalation occurred in 69/124 patients. Erlotinib was well tolerated with 70% of patients developing a grade 1/2 rash and 10% developing grade 3 rash. Response rate and disease control rate were 6.5% and 41.1% respectively. Median overall survival was 7.7 months. Toxicity and tumour markers were not associated with response. Grade 2 or greater skin rash and low phosphorylated mitogen-activated protein kinase (pMAPK) were associated with improved survival. Conclusions: Overall survival was similar in this trial compared to first-line chemotherapy in this unselected patient population. Dose escalation to the development of grade 2 skin rash was associated with improved survival in this patient population. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Brahmer, J. R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Lee, J. W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Traynor, A. M.; Kolesar, J. M.] Univ Wisconsin, Madison, WI USA. [Hidalgo, M. M.] Hosp Madrid Sanchinarro, Madrid, Spain. [Siegfried, J. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Guaglianone, P. P.] Decatur Mem Hosp, Decatur, IL USA. [Patel, J. D.] Northwestern Univ, Chicago, IL 60611 USA. [Keppen, M. D.] Sanford Canc Ctr, Sioux Falls, SD USA. [Schiller, J. H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Brahmer, JR (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Bunting Blaustein Canc Res Bldg,Room G94, Baltimore, MD 21287 USA. EM brahmju@jhmi.edu RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU Public Health Service [CA23318, CA66636, CA21115, CA21076, CA16116, CA39229, CA17145]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA21076, CA16116, CA39229, CA17145 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 23 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2014 VL 50 IS 2 BP 302 EP 308 DI 10.1016/j.ejca.2013.10.006 PG 7 WC Oncology SC Oncology GA 293PV UT WOS:000329986500006 PM 24246704 ER PT J AU Hong, NJL Chang, SL Raut, CP AF Hong, Nicole J. Look Chang, Steven L. Raut, Chandrajit P. TI The economic impact of cytoreductive surgery and tyrosine kinase inhibitor therapy in the treatment of advanced gastrointestinal stromal tumours: A Markov chain decision analysis SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE GIST; Sarcoma; Surgery; Cost; Cytoreduction ID MULTICENTER PHASE-II; SOFT-TISSUE SARCOMAS; IMATINIB MESYLATE; ADVANCED/METASTATIC GIST; SURGICAL RESECTION; COST-EFFECTIVENESS; UNITED-STATES; SUNITINIB; TRIAL; PROGRESSION AB Purpose: The current first-line treatment for patients with recurrent or metastatic gastrointestinal stromal tumours (GIST) is management with tyrosine kinase inhibition (TKI). There is an undefined role for surgery in the management of these patients. This study uses a cost analysis to examine the economic impact of treating patients with TKI in combination with surgery at different time-points in their treatment trajectories. Methods: A Markov chain decision analysis was modelled over a 2-year time horizon to determine costs associated with surgery in combination with imatinib mesylate (IM) or sunitinib malate (SU) in seven scenarios varied by TKI agent, dose and disease status (stable versus localised progressive disease). Rates of disease progression, surgical morbidity, mortality and adverse drug reactions were extracted from the existing literature. Deterministic sensitivity analyses were performed to examine changes in cost due to variations in key variables. Results: The least-costly scenario was to perform no surgery. The most costly scenario was to perform surgery on patients with localised progressive disease on IM 800 mg. The overall range of costs clustered within approximately $47,000 (USD). Variations in surgical cost, surgical mortality and cost of IM demonstrated thresholds for changing the least-costly scenario within plausible tested ranges. Conclusion: Costs of surgical intervention at different time-points within the treatment course of patients with advanced GIST fluctuate within a relatively narrow range, suggesting that costs arise primarily from the administration of TKI. The decision to pursue cytoreductive surgery should not be based on cost alone. Future studies should incorporate health-state utilities when available. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hong, Nicole J. Look; Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Ctr Sarcoma & Bone Oncol, Div Surg Oncol,Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Chang, Steven L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Oncol,Med Sch, Boston, MA 02115 USA. RP Hong, NJL (reprint author), Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM n.lookhong@utoronto.ca NR 38 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2014 VL 50 IS 2 BP 397 EP 405 DI 10.1016/j.ejca.2013.08.026 PG 9 WC Oncology SC Oncology GA 293PV UT WOS:000329986500016 ER PT J AU De Luca, G van't Hof, AWJ Huber, K Gibson, CM Bellandi, F Arntz, HR Maioli, M Noc, M Zorman, S Secco, GG Zeymer, U Gabriel, HM Emre, A Cutlip, D Rakowski, T Gyongyosi, M Dudek, D AF De Luca, Giuseppe van't Hof, Arnoud W. J. Huber, Kurt Gibson, C. Michael Bellandi, Francesco Arntz, Hans-Richard Maioli, Mauro Noc, Marko Zorman, Simona Secco, Gioel Gabrio Zeymer, Uwe Mesquita Gabriel, H. Emre, Ayse Cutlip, Donald Rakowski, Tomasz Gyongyosi, Maryann Dudek, Dariusz TI Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors SO HEART AND VESSELS LA English DT Article DE Primary angioplasty; Perfusion; Elderly; Mortality ID PERCUTANEOUS CORONARY INTERVENTION; LEFT-VENTRICULAR FUNCTION; IN-HOSPITAL MORTALITY; ISCHEMIA-REPERFUSION; RANDOMIZED-TRIALS; ELDERLY-PATIENTS; BLUSH GRADE; NO-REFLOW; METAANALYSIS; THERAPY AB Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb-IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb-IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb-IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0-2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0-1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31-6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63-9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality. C1 [De Luca, Giuseppe; Secco, Gioel Gabrio] Eastern Piedmont Univ, Maggiore Carita Hosp, Div Cardiol, Novara, Italy. [van't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. [Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med Cardiol & Emergency Med, Vienna, Austria. [Gibson, C. Michael] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Bellandi, Francesco; Maioli, Mauro] Prato Hosp, Div Cardiol, Prato, Italy. [Arntz, Hans-Richard] Charite, Med Klin 2, Berlin, Germany. [Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [Mesquita Gabriel, H.] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Istanbul, Turkey. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Rakowski, Tomasz; Dudek, Dariusz] Jagiellonian Univ, Inst Cardiol, Dept Cardiol 2, Krakow, Poland. [Gyongyosi, Maryann] Med Univ Vienna, Dept Cardiol, Vienna, Austria. RP Secco, GG (reprint author), Eastern Piedmont Univ, Maggiore Carita Hosp, Div Cardiol, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it; gioel.gabrio.secco@gmail.com NR 33 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0910-8327 EI 1615-2573 J9 HEART VESSELS JI Heart Vessels PD JAN PY 2014 VL 29 IS 1 BP 15 EP 20 DI 10.1007/s00380-013-0323-4 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 292ZZ UT WOS:000329942500003 PM 23494604 ER PT B AU Murray, D AF Murray, David BE Rahko, PS TI Left Ventricular Dysfunction and Associated Renal Failure: The Cardiorenal Syndrome SO HEART FAILURE: A CASE-BASED APPROACH LA English DT Article; Book Chapter ID DECOMPENSATED HEART-FAILURE; VENOUS-PRESSURE; INTRAABDOMINAL PRESSURE; ULTRAFILTRATION; DIURETICS; MORTALITY; DOPAMINE; NESIRITIDE; KIDNEY; DEATH C1 [Murray, David] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Murray, David] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Murray, David] William S Middleton Mem Vet Adm Med Ctr, Cardiol Sect, Madison, WI USA. RP Murray, D (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. NR 45 TC 0 Z9 0 U1 0 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-51-2 PY 2014 BP 229 EP 239 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BJL42 UT WOS:000328866100017 ER PT J AU Neilan, TG Mongeon, FP Shah, RV Coelho, O Abbasi, SA Dodson, JA McMullan, CJ Heydari, B Michaud, GF John, RM Blankstein, R Jerosch-Herold, M Kwong, RY AF Neilan, Tomas G. Mongeon, Francois-Pierre Shah, Ravi V. Coelho-Filho, Otavio Abbasi, Siddique A. Dodson, John A. McMullan, Ciaran J. Heydari, Bobak Michaud, Gregory F. John, Roy M. Blankstein, Ron Jerosch-Herold, Michael Kwong, Raymond Y. TI Myocardial Extracellular Volume Expansion and the Risk of Recurrent Atrial Fibrillation After Pulmonary Vein Isolation SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; myocardial fibrosis; T-1 measurements ID CARDIOVASCULAR MAGNETIC-RESONANCE; LEFT-VENTRICULAR MASS; HYPERTENSIVE HEART-DISEASE; DIASTOLIC DYSFUNCTION; MATRIX EXPANSION; FIBROSIS; HYPERTROPHY; ASSOCIATION; FAILURE; ECHOCARDIOGRAPHY AB OBJECTIVES This study tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether there is an association between ECV and post-procedural recurrence of AF. BACKGROUND Hypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T-1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV. METHODS Consecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF. RESULTS Patients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 +/- 0.03; healthy control patients, 0.29 +/- 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation [E'] r = -0.55, p < 0.001). In the best overall multivariable model, ECV was the strongest predictor of the primary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p < 0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF. CONCLUSIONS In patients with AF and hypertension, expansion of ECV is associated with diastolic function and left atrial remodeling and is a strong independent predictor of recurrent AF post-pulmonary vein isolation. (C) 2014 by the American College of Cardiology Foundation C1 [Neilan, Tomas G.; Mongeon, Francois-Pierre; Shah, Ravi V.; Coelho-Filho, Otavio; Abbasi, Siddique A.; Heydari, Bobak; Michaud, Gregory F.; John, Roy M.; Blankstein, Ron; Kwong, Raymond Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Neilan, Tomas G.; Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Div Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. [Mongeon, Francois-Pierre] Univ Montreal, Montreal Heart Inst, Dept Med, Montreal, PQ, Canada. [Coelho-Filho, Otavio] State Univ Campinas UNICAMP, Dept Internal Med, Campinas, SP, Brazil. [Dodson, John A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [McMullan, Ciaran J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Nephrol, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Kwong, RY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. EM rykwong@partners.org OI Abbasi, Siddique/0000-0002-9601-7565 FU National Institutes of Health [T32 AG000158-24, R01HL090634, R01HL091157]; American Heart Association [12FTF12060588] FX From the *Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; dagger Division of Cardiology, Department of Medicine, Cardiac MR PET CT Program, Division of Radiology, Massachusetts General Hospital, Boston, Massachusetts; double dagger Department of Medicine, Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada; (Department of Internal Medicine, State University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil; (Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Nephrology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and the #Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Dr.Neilan has received an American Heart Association Fellow to Faculty Grant (12FTF12060588). Dr. Shah has received minor consulting fees from Novartis and VentriPoint. Dr. Abbasi has received funding from the National Institutes of Health (T32 fellowship). Dr. Dodson has received funding from the National Institutes of Health (T32 AG000158-24) during the writing of this manuscript. Dr. Michaud has received honoraria from Boston Scientific and Medtronic. Dr. John has received honoraria from St. Jude Medical. Dr. Jerosch-Herold has received research support from the National Institutes of Health (R01HL090634). Dr. Kwong has received research support from the National Institutes of Health (R01HL091157). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 47 TC 18 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2014 VL 7 IS 1 BP 1 EP 11 DI 10.1016/j.jcmg.2013.08.013 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 293EF UT WOS:000329953500001 PM 24290570 ER PT J AU Hruby, A O'Donnell, CJ Jacques, PF Meigs, JB Hoffmann, U McKeown, NM AF Hruby, Adela O'Donnell, Christopher J. Jacques, Paul F. Meigs, James B. Hoffmann, Udo McKeown, Nicola M. TI Magnesium Intake Is Inversely Associated With Coronary Artery Calcification SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE abdominal aortic calcification; computed tomography; coronary artery calcification; diet; Framingham Heart Study; magnesium ID DIETARY MAGNESIUM; CARDIOVASCULAR-DISEASE; ATHEROSCLEROTIC PLAQUE; RISK-FACTORS; HEART; CALCIUM; SERUM; CONSUMPTION; MORTALITY; INSULIN AB OBJECTIVES The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying cardiovascular disease. Little is known about the association of magnesium intake and atherosclerotic calcification in humans. METHODS We examined cross-sectional associations of self-reported total (dietary and supplemental) magnesium intake estimated by food frequency questionnaire with CAC and AAC in participants of the Framingham Heart Study who were free of cardiovascular disease and underwent Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695; age: 53 11 years), using multivariate-adjusted Tobit regression. CAC and AAC were quantified using modified Agatston scores (AS). Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, fasting insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone replacement therapy (women only), menopausal status (women only), treatment for hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber, alcohol, and energy. Secondary analyses included logistic regressions of CAC and AAC outcomes as cut-points (AS >0 and AS >= 90th percentile for age and sex), as well as sex-stratified analyses. RESULTS In fully adjusted models, a 50-mg/day increment in self-reported total magnesium intake was associated with 22% lower CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations, the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34% lower (p trend: 0.01), in those with the highest compared to those with the lowest magnesium intake. Stronger inverse associations were observed in women than in men. CONCLUSIONS In community-dwelling participants free of cardiovascular disease, self-reported magnesium intake was inversely associated with arterial calcification, which may play a contributing role in magnesium's protective associations in stroke and fatal coronary heart disease. (C) 2014 by the American College of Cardiology Foundation C1 [Hruby, Adela; Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA. [O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Meigs, James B.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP McKeown, NM (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, 711 Washington St,9th Floor, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; American Heart Association Predoctoral Fellowship; United States Department of Agriculture (USDA) [58-1950-0-014]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK080140] FX From the *Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts; dagger National Heart, Lung, and Blood Institute (NHLBI) Division of Intramural Research, and NHLBI's Framingham Heart Study, Framingham, Massachusetts; double dagger Cardiovascular Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; (General Medicine Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; and the Massachusetts General Hospital Cardiac MR PET CT Program and the Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. At the time of writing, Dr. Hruby was supported by an American Heart Association Predoctoral Fellowship. This work was also supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195) and the United States Department of Agriculture (USDA agreement no. 58-1950-0-014). Dr. Jacques has been a member of the Bay State Milling Nutrition Science Advisory Council and of the Dannon Yogurt Advisory Board. Dr. Meigs is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (K24 DK080140). All authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 49 TC 28 Z9 30 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2014 VL 7 IS 1 BP 59 EP 69 DI 10.1016/j.jcmg.2013.10.006 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 293EF UT WOS:000329953500009 PM 24290571 ER PT J AU Iskandrian, AE Hage, FG Shaw, LJ Mahmarian, JJ Berman, DS AF Iskandrian, Ami E. Hage, Fadi G. Shaw, Leslee J. Mahmarian, John J. Berman, Daniel S. TI Serial Myocardial Perfusion Imaging Defining a Significant Change and Targeting Management Decisions SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE coronary artery disease; myocardial ischemia; myocardial perfusion imaging; single-photon emission tomography; stress testing ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; INTENSIVE MEDICAL THERAPY; LEFT-VENTRICULAR FUNCTION; PLACEBO-CONTROLLED TRIAL; QUANTITATIVE-ANALYSIS; EXERCISE ELECTROCARDIOGRAPHY; NUCLEAR CARDIOLOGY; ISCHEMIA DETECTION AB Myocardial perfusion imaging (MPI) with gated single-photon emission tomography provides important information on the extent and severity of myocardial perfusion abnormalities, including myocardial ischemia. The availability of software for automated quantitative assessment of myocardial perfusion in an objective and more reproducible manner than visual assessment has allowed MPI to be particularly effective in serial evaluation. Serial testing using MPI is widely used in guiding patient care despite the lack of well-defined appropriateness use criteria. This should not be surprising because ischemic heart disease is a life-long malady subject to dynamic changes throughout its natural course and particularly following man-made interventions that may improve or worsen the disease process, such as medical therapy and coronary revascularization. Serial MPI has filled an important clinical gap by providing crucial information for managing patients with changes in clinical presentations or in anticipation of such changes in patients with stable symptoms. In the research arena, serial MPI has been widely applied in randomized controlled trials to study the impact of various medical and interventional therapies on myocardial perfusion, as well as the relative merits of new imaging procedures (hardware and/or software), radiotracers, and stressor agents. Serial testing, however, unlike initial or 1-time testing, has more stringent requirements and is subject to variability because of technical, procedural, interpretational, and biological factors. The intrinsic variability of MPI becomes important in interpreting serial tests in order to define a true change in a given patient and to guide clinical decision making. The purpose of this first comprehensive review on this subject is to illustrate where serial MPI may be useful clinically and in research studies, and to highlight strategies for addressing the various issues that are unique to serial testing in order to derive more valid and robust data from the serial scans. (C) 2014 by the American College of Cardiology Foundation C1 [Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35242 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA. [Mahmarian, John J.] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Iskandrian, AE (reprint author), Univ Alabama Birmingham, Div Cardiol, Dept Med, 318 LHRB,1900 Univ Blvd, Birmingham, AL 35242 USA. EM aiskand@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 58 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JAN PY 2014 VL 7 IS 1 BP 79 EP 96 DI 10.1016/j.jcmg.2013.05.022 PG 18 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 293EF UT WOS:000329953500011 PM 24433711 ER PT J AU Goldbogen, JA Meir, JU AF Goldbogen, Jeremy A. Meir, Jessica U. TI The device that revolutionized marine organismal biology SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Editorial Material ID WEDDELL SEAL; PREDATOR; CALIFORNIA; BEHAVIOR; HYPOXIA; MAMMALS; OCEAN; SOUND C1 [Goldbogen, Jeremy A.] Stanford Univ, Stanford, CA 94305 USA. [Meir, Jessica U.] NASA, Johnson Space Ctr, Kennedy Space Ctr, FL USA. [Meir, Jessica U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Goldbogen, JA (reprint author), Stanford Univ, Stanford, CA 94305 USA. EM jergold@stanford.edu; jmeir@mgh.harvard.edu OI Goldbogen, Jeremy/0000-0002-4170-7294 NR 20 TC 1 Z9 1 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD JAN PY 2014 VL 217 IS 2 BP 167 EP 168 DI 10.1242/jeb.092189 PG 2 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 291VX UT WOS:000329860800011 PM 24431140 ER PT J AU Turalba, AV Shah, AS Andreoli, MT Andreoli, CM Rhee, DJ AF Turalba, Angela V. Shah, Ankoor S. Andreoli, Michael T. Andreoli, Christopher M. Rhee, Douglas J. TI Predictors and Outcomes of Ocular Hypertension After Open-globe Injury SO JOURNAL OF GLAUCOMA LA English DT Article DE eye trauma; open-globe injury; glaucoma; traumatic glaucoma ID GLAUCOMA; TRAUMA; REGISTRY; COHORT AB Purpose:Evaluate predictors and outcomes of ocular hypertension after open-globe injury.Patients and Methods:This is a retrospective, case-control study reviewing records of consecutive patients with open-globe injuries treated at Massachusetts Eye and Ear Infirmary between February 1999 and January 2007. Of 658 patients treated, 382 had at least 2 months of follow-up and sufficient data to be included. Main outcome measures are visual acuity, intraocular pressure (IOP), and type of glaucoma intervention employed.Results:Sixty-five (17%) patients developed ocular hypertension defined as IOP22 mm Hg at >1 visit or requiring treatment. Increased age (P<0.001), hyphema (0.025), lens injury (P<0.0001), and zone II injury (P=0.0254) are risk factors for developing ocular hypertension after open-globe injury. Forty-eight (74%) patients with ocular hypertension were treated medically, 8 (12%) underwent filtering or glaucoma drainage device surgery, 5 (8%) had IOP normalization with observation, while 4 (6%) required anterior chamber washout with no other glaucoma surgery. Patients with ocular hypertension had an average maximum IOP=33.4 mm Hg at a median follow-up of 21 days, with most patients maintaining normal IOP at all follow-up time points. Visual acuity improved over time with median acuity of hand motions preoperatively, and 20/60 at 12 and 36 months.Conclusions:Ocular hypertension is a significant complication after open-globe injury that sometimes requires surgical intervention. Predictive factors can alert physicians to monitor for elevated IOP in the first month after trauma. Most patients with traumatic ocular hypertension had improved visual acuity and IOP normalization over time. C1 [Turalba, Angela V.; Shah, Ankoor S.; Andreoli, Christopher M.; Rhee, Douglas J.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Turalba, Angela V.; Shah, Ankoor S.; Andreoli, Christopher M.; Rhee, Douglas J.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Turalba, Angela V.] VA Boston Healthcare Syst, Dept Ophthalmol, Boston, MA USA. [Shah, Ankoor S.; Rhee, Douglas J.] Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Andreoli, Michael T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Andreoli, Christopher M.] Harvard Vanguard Med Associates, Dept Ophthalmol, Boston, MA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 16 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD JAN PY 2014 VL 23 IS 1 BP 5 EP 10 DI 10.1097/IJG.0b013e318265bb4a PG 6 WC Ophthalmology SC Ophthalmology GA 291CL UT WOS:000329805200003 PM 22936278 ER PT J AU Saeedi, OJ Jefferys, JL Solus, JF Jampel, HD Quigley, HA AF Saeedi, Osamah J. Jefferys, Joan L. Solus, Jason F. Jampel, Henry D. Quigley, Harry A. TI Risk Factors for Adverse Consequences of Low Intraocular Pressure After Trabeculectomy SO JOURNAL OF GLAUCOMA LA English DT Article DE trabeculectomy; hypotony maculopathy; hypotony; choroidal detachment ID GLAUCOMA FILTERING SURGERY; BLEB-RELATED COMPLICATIONS; CENTRAL CORNEAL THICKNESS; MITOMYCIN-C; HYPOTONY MACULOPATHY; OPEN-ANGLE; SUBCONJUNCTIVAL 5-FLUOROURACIL; FOLLOW-UP; OUTCOMES; CLOSURE AB Purpose:To determine the risk factors for low intraocular pressure (IOP) and its detrimental consequences after trabeculectomy.Patients and Methods:We performed a retrospective chart review of consecutive patients aged 12 years and above undergoing trabeculectomy alone by 1 of 2 surgeons between May 2000 and October 2008 at the Wilmer Institute.Results:Among 753 eyes of 596 patients, 112 eyes (14.9%) of 103 patients had an IOP of 5 mm Hg at 3 months postoperatively (late low IOP). Physical signs related to low IOP occurred in 61 eyes of 58 patients, and 40 eyes of 37 patients had revision surgery for low IOP. Physical signs of low IOP included 34 eyes with choroidal detachment or shallow anterior chamber, 10 with hypotony maculopathy, and 7 with both. Compared with 187 control eyes of 165 patients, risk factors for late low IOP included: surgeon 2 (P=0.0003), left eyes (P=0.03), and secondary glaucoma (P=0.05). Physical signs of low IOP were more common in phakic eyes (P=0.03), whereas need for revision surgery was associated with younger age (P=0.01). The presence of hypotony maculopathy significantly decreased the risk of choroidal detachment/shallow anterior chamber (P=0.003). Hypotony maculopathy was associated with younger age (P=0.02).Conclusions:Late low IOP was more common with techniques used by 1 of 2 surgeons and in eyes with secondary glaucoma. Clinical signs of low IOP were more common in phakic eyes. Younger age was a risk factor for hypotony maculopathy. Hypotony maculopathy and choroidal detachment tend to occur in different eyes. C1 [Saeedi, Osamah J.] Univ Maryland, Sch Med, Dept Ophthalmol & Visual Sci, Baltimore, MD 21201 USA. [Jefferys, Joan L.; Jampel, Henry D.; Quigley, Harry A.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Solus, Jason F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Solus, Jason F.] Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Glaucoma Ctr Excellence, Baltimore, MD 21205 USA. RP Saeedi, OJ (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol & Visual Sci, 419 W Redwood St,Suite 479, Baltimore, MD 21201 USA. EM osaeedi@som.umaryland.edu NR 36 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD JAN PY 2014 VL 23 IS 1 BP E60 EP E68 DI 10.1097/IJG.0000000000000008 PG 9 WC Ophthalmology SC Ophthalmology GA 291CL UT WOS:000329805200023 PM 24145291 ER PT J AU Erpelding, N Sava, S Simons, LE Lebel, A Serrano, P Becerra, L Borsook, D AF Erpelding, Nathalie Sava, Simona Simons, Laura E. Lebel, Alyssa Serrano, Paul Becerra, Lino Borsook, David TI Habenula functional resting-state connectivity in pediatric CRPS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE resting state; functional connectivity; CRPS; chronic pain; pediatric ID REGIONAL PAIN SYNDROME; DIABETIC NEUROPATHIC PAIN; DORSOLATERAL PREFRONTAL CORTEX; MEDIATED CHRONIC PAIN; DEFAULT-MODE NETWORK; STRUCTURAL CONNECTIVITY; LATERAL HABENULA; CORTICAL REORGANIZATION; PERIAQUEDUCTAL GRAY; SUBSTANTIA-NIGRA AB The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric pzand sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology. C1 [Erpelding, Nathalie; Sava, Simona; Simons, Laura E.; Lebel, Alyssa; Serrano, Paul; Becerra, Lino; Borsook, David] Childrens Hosp Boston, PAIN Grp, Waltham, MA USA. [Erpelding, Nathalie; Sava, Simona; Simons, Laura E.; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Becerra, Lino; Borsook, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Becerra, Lino; Borsook, David] McLean Hosp, Belmont, MA 02178 USA. RP Erpelding, N (reprint author), Harvard Univ, Sch Med, Ctr Pain & Brain, PAIN Grp,Boston Childrens Hosp, 9 Hope Ave, Waltham, MA 02453 USA. EM nathalie.erpelding@childrens.harvard.edu FU National Institute of Neurological Disorders and Stroke [R01-NS-065051, K24-NS-064050]; National Institute of Child Health and Human Development K23 Career Development Award [HD-067202]; Mayday Foundation, New York FX This study was primarily supported by National Institute of Neurological Disorders and Stroke Grants R01-NS-065051 and K24-NS-064050 (to D. Borsook), by National Institute of Child Health and Human Development K23 Career Development Award HD-067202 (to L. E. Simons), and by a Grant from the Mayday Foundation, New York. NR 87 TC 11 Z9 11 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2014 VL 111 IS 2 BP 239 EP 247 DI 10.1152/jn.00405.2013 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 292SM UT WOS:000329922600002 PM 24155006 ER PT J AU Alam, MA Kumar, S McGinty, D Alam, MN Szymusiak, R AF Alam, Md. Aftab Kumar, Sunil McGinty, Dennis Alam, Md. Noor Szymusiak, Ronald TI Neuronal activity in the preoptic hypothalamus during sleep deprivation and recovery sleep SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE adenosine; median preoptic nucleus; REM sleep; sleep homeostasis; ventrolateral preoptic area ID EYE-MOVEMENT SLEEP; BASAL FOREBRAIN NEURONS; PERIFORNICAL LATERAL HYPOTHALAMUS; VENTROLATERAL PERIAQUEDUCTAL GRAY; WAKING DISCHARGE PATTERNS; FOS PROTEIN EXPRESSION; GABAERGIC NEURONS; C-FOS; REM-SLEEP; HOMEOSTATIC REGULATION AB The preoptic hypothalamus is implicated in sleep regulation. Neurons in the median preoptic nucleus (MnPO) and the ventrolateral preoptic area (VLPO) have been identified as potential sleep regulatory elements. However, the extent to which MnPO and VLPO neurons are activated in response to changing homeostatic sleep regulatory demands is unresolved. To address this question, we continuously recorded the extracellular activity of neurons in the rat MnPO, VLPO and dorsal lateral preoptic area (LPO) during baseline sleep and waking, during 2 h of sleep deprivation (SD) and during 2 h of recovery sleep (RS). Sleep-active neurons in the MnPO (n = 11) and VLPO (n = 13) were activated in response to SD, such that waking discharge rates increased by 95.8 +/- 29.5% and 59.4 +/- 17.3%, respectively, above waking baseline values. During RS, non-rapid eye movement (REM) sleep discharge rates of MnPO neurons initially increased to 65.6 +/- 15.2% above baseline values, then declined to baseline levels in association with decreases in EEG delta power. Increase in non-REM sleep discharge rates in VLPO neurons during RS averaged 40.5 +/- 7.6% above baseline. REM-active neurons (n = 16) in the LPO also exhibited increased waking discharge during SD and an increase in non-REM discharge during RS. Infusion of A(2A) adenosine receptor antagonist into the VLPO attenuated SD-induced increases in neuronal discharge. Populations of LPO wake/REM-active and state-indifferent neurons and dorsal LPO sleep-active neurons were unresponsive to SD. These findings support the hypothesis that sleep-active neurons in the MnPO and VLPO, and REM-active neurons in the LPO, are components of neuronal circuits that mediate homeostatic responses to sustained wakefulness. C1 [Alam, Md. Aftab; Kumar, Sunil; McGinty, Dennis; Alam, Md. Noor; Szymusiak, Ronald] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA USA. [McGinty, Dennis] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Alam, Md. Noor; Szymusiak, Ronald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Szymusiak, Ronald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucla.edu FU Department of Veterans Affairs; National Institute of Mental Health [MH-63323] FX This study was supported by the Department of Veterans Affairs and National Institute of Mental Health Grant MH-63323. NR 55 TC 12 Z9 13 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2014 VL 111 IS 2 BP 287 EP 299 DI 10.1152/jn.00504.2013 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 292SM UT WOS:000329922600006 PM 24174649 ER PT J AU Hamilton, TE Barnhart, D Gow, K Ferrer, F Kandel, J Glick, R Dasgupta, R Naranjo, A He, Y Gratias, E Geller, J Mullen, E Ehrlich, P AF Hamilton, Thomas E. Barnhart, Douglas Gow, Kenneth Ferrer, Fernando Kandel, Jessica Glick, Richard Dasgupta, Roshni Naranjo, Arlene He, Ying Gratias, Eric Geller, James Mullen, Elizabeth Ehrlich, Peter TI Inter-rater reliability of surgical reviews for AREN03B2: A COG renal tumor committee study SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Wilms Tumor; Quality assurance; Surgery; Outcomes ID NATIONAL WILMS-TUMOR AB Purpose: The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews. Methods: Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value). Results: Local tumor stage correlated in all 3 reviews except in one case (Kappa - 0.9775, p < 0.001). Similarly, overall disease stage had excellent correlation (0.9422, p <0.001). There was strong correlation for type of renal procedure (0.8357, p < 0.001), presence of tumor rupture (0.6858, p < 0.001), intraoperative tumor spill (0.6493, p< 0.001), and blood vessel involvement (0.6470, p < 0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p < 0.001) and interpretation of residual disease status (0.5310, p < 0.001). Conclusion: The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hamilton, Thomas E.; Mullen, Elizabeth] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02118 USA. [Barnhart, Douglas] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Gow, Kenneth] Seattle Childrens Hosp, Seattle, WA USA. [Ferrer, Fernando] Connecticut Childrens Hosp, Hartford, CT USA. [Kandel, Jessica] Columbia Univ, Med Ctr, New York, NY USA. [Glick, Richard] Cohen Childrens Med Ctr New York, New York, NY USA. [Dasgupta, Roshni] Cinncinnati Childrens Hosp, Cincinnati, OH USA. [Naranjo, Arlene; He, Ying] Univ Florida, Childrens Oncol Grp, Gainesville, FL USA. [Gratias, Eric] TC Thompson Childrens Hosp, Chattanooga, TN USA. [Geller, James] Cincinnati Childrens Hosp, Cincinnati Med Ctr, Cincinnati, OH USA. [Ehrlich, Peter] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. RP Hamilton, TE (reprint author), Boston Childrens Hosp, Dept Surg, 1 Boston Med Ctr Pl,Dowling 2 South, Boston, MA 02118 USA. EM thomas.hamilton@childrens.harvard.edu FU NIH [U10 CA98413, U10 CA98543] FX This work was supported by NIH grants U10 CA98413 (COG SDC grant) and U10 CA98543 (COG Chair's grant). NR 14 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2014 VL 49 IS 1 BP 154 EP 158 DI 10.1016/j.jpedsurg.2013.09.047 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 291SI UT WOS:000329849200030 PM 24439601 ER PT J AU Hildenbrand, AK Alderfer, MA Deatrick, JA Marsac, ML AF Hildenbrand, Aimee K. Alderfer, Melissa A. Deatrick, Janet A. Marsac, Meghan L. TI A Mixed Methods Assessment of Coping with Pediatric Cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE coping; coping assistance; pediatric cancer; mixed methods; childhood cancer ID MEDICAL PROCEDURES; CHILDREN; STRESS; ADOLESCENTS; ADJUSTMENT; SYMPTOMS; STRATEGIES; DISTRESS; AVOIDANT; PARENTS AB The purpose of this study was to describe child coping and parent coping assistance with cancer-related stressors during treatment. Fifteen children (age 6-12) with cancer and their parents (N = 17) completed semistructured interviews and self-report measures to assess coping and coping assistance. Results suggest families utilized a broad array of approach and avoidance strategies to manage cancer and its treatment. Quantitative and qualitative assessments provided complementary and unique contributions to understanding coping among children with cancer and their parents. Using a mixed methods approach to assess coping provides a richer understanding of families' experiences, which can better inform clinical practice. C1 [Hildenbrand, Aimee K.; Marsac, Meghan L.] Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, Philadelphia, PA 19104 USA. [Alderfer, Melissa A.] Childrens Hosp Philadelphia, Ctr Canc, Philadelphia, PA 19104 USA. [Alderfer, Melissa A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Hildenbrand, AK (reprint author), Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, 3535 Market,Suite 1150, Philadelphia, PA 19104 USA. EM hildenbranda@email.chop.edu FU NIMH NIH HHS [K23 MH093618, 1K23MH093618-01A1] NR 67 TC 5 Z9 5 U1 2 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 EI 1540-7586 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PD JAN 1 PY 2014 VL 32 IS 1 BP 37 EP 58 DI 10.1080/07347332.2013.855960 PG 22 WC Psychology, Social SC Psychology GA 289NI UT WOS:000329688800002 PM 24428250 ER PT J AU Knox, ADC Reddy, S Mema, B DeMoya, M Cilli-Turner, E Harris, I AF Knox, Aaron D. C. Reddy, Shalini Mema, Briseida DeMoya, Marc Cilli-Turner, Emily Harris, Ilene TI "Back in the Day" ... What are Surgeon Bloggers Saying About Their Careers? SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE blogging; surgery; qualitative research; professional burnout; career choice; workforce ID GENERAL-SURGERY; SATISFACTION; BLOGOSPHERE; BLOGS AB OBJECTIVES: The projected shortage of general surgeons is owing to an increased demand for surgical services and a declining pool of practicing general surgeons. Burnout and attrition of residents from surgical residencies contribute to the latter. Attrition may be caused by the choice of a career in surgery without an understanding of the realities; subsequent recognition of the realities may cause residents to reexamine the opportunity costs of a career in the field. Because weblogs (blogs) are often used for reflection, qualitative analysis of the content of blogs authored by general surgeons may provide insight into the positive and negative realities of a surgical career. These insights may be informative to students as they consider a surgical career, may better prepare residents for the reality of what is to come, and identify targets for improving the culture of surgery and mitigating sources of career dissatisfaction. DESIGN: This is a qualitative analysis of entries on blogs authored by practicing general surgeons. A systematic approach was used to identify a sample of blog posts. These posts were analyzed using a constant comparative analysis method associated with constructivist grounded theory. RESULTS: Thirty-five posts drawn from 9 blogs were analyzed. Five main themes were identified in the reviewed blogs. Overall, 104 comments were positive in tone, 74 were neutral, and 147 were negative. There were 96 comments that focused on the rewards of being a surgeon, 88 concerning the practice environment, 57 about the educational environment, 54 about the toll of being a surgeon, and 30 pertaining to nostalgia. The most commonly identified subthemes focused on the training experience (38 comments), a surgical career providing personal fulfillment (35 comments), the impact of the culture of surgery (33 comments), and financial concerns (30 comments). A conceptual framework focused on balance was used to explain how the themes relate to each other. CONCLUSIONS: Themes identified are consistent with prior studies about surgeon career satisfaction. The considerable rewards of being a surgeon were outweighed by the challenges encountered in day-to-day practice. Meeting societal needs for more general surgeons would require efforts to minimize the tolls, to the extent possible, while encouraging individuals drawn to the rewarding work of being a surgeon. (C) 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Knox, Aaron D. C.] Univ British Columbia, Vancouver Gen Hosp, Div Plast Surg, Vancouver, BC V5Z 1M9, Canada. [Reddy, Shalini] Univ Chicago, Sect Hosp Med, Dept Internal Med, Chicago, IL 60637 USA. [Mema, Briseida] Hosp Sick Children, Dept Crit Care Med, Toronto, ON M5G 1X8, Canada. [DeMoya, Marc] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Cilli-Turner, Emily] Univ Illinois, Dept Math Stat & Comp Sci, Chicago, IL 60680 USA. [Harris, Ilene] Univ Illinois, Dept Med Educ, Chicago, IL USA. RP Knox, ADC (reprint author), Toronto Gen Hosp, Wilson Ctr, 200 Elizabeth St,1st Floor Eaton South Room 559, Toronto, ON M5G 2C4, Canada. EM aknox@ualberta.ca RI guo, iris/P-3439-2015 NR 62 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD JAN-FEB PY 2014 VL 71 IS 1 BP 21 EP 31 DI 10.1016/j.jsurg.2013.04.005 PG 11 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA 293DH UT WOS:000329951100010 PM 24411419 ER PT J AU Wayne, PM Walsh, JN Taylor-Piliae, RE Wells, RE Papp, KV Donovan, NJ Yeh, GY AF Wayne, Peter M. Walsh, Jacquelyn N. Taylor-Piliae, Ruth E. Wells, Rebecca E. Papp, Kathryn V. Donovan, Nancy J. Yeh, Gloria Y. TI Effect of Tai Chi on Cognitive Performance in Older Adults: Systematic Review and Meta-Analysis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Tai Chi; cognitive function; executive function; mind-body exercise ID RANDOMIZED-CONTROLLED-TRIAL; FUNCTIONAL PLASTICITY; BRAIN VOLUME; EXERCISE; DEMENTIA; MEMORY; HIPPOCAMPUS; COMMUNITY; RISK; INTERVENTION AB ObjectivesTo summarize and critically evaluate research on the effects of Tai Chi on cognitive function in older adults. DesignSystematic review with meta-analysis. SettingCommunity and residential care. ParticipantsIndividuals aged 60 and older (with the exception of one study) with and without cognitive impairment. MeasurementsCognitive ability using a variety of neuropsychological testing. ResultsTwenty eligible studies with a total of 2,553 participants were identified that met inclusion criteria for the systematic review; 11 of the 20 eligible studies were randomized controlled trials (RCTs), one was a prospective nonrandomized controlled study, four were prospective noncontrolled observational studies, and four were cross-sectional studies. Overall quality of RCTs was modest, with three of 11 trials categorized as high risk of bias. Meta-analyses of outcomes related to executive function in RCTs of cognitively healthy adults indicated a large effect size when Tai Chi participants were compared with nonintervention controls (Hedges' g=0.90; P=.04) and a moderate effect size when compared with exercise controls (Hedges' g=0.51; P=.003). Meta-analyses of outcomes related to global cognitive function in RCTs of cognitively impaired adults, ranging from mild cognitive impairment to dementia, showed smaller but statistically significant effects when Tai Chi was compared with nonintervention controls (Hedges' g=0.35; P=.004) and other active interventions (Hedges' g=0.30; P=.002). Findings from nonrandomized studies add further evidence that Tai Chi may positively affect these and other domains of cognitive function. ConclusionTai Chi shows potential to enhance cognitive function in older adults, particularly in the realm of executive functioning and in individuals without significant impairment. Larger and methodologically sound trials with longer follow-up periods are needed before more-definitive conclusions can be drawn. C1 [Wayne, Peter M.; Walsh, Jacquelyn N.] Brigham & Womens Hosp, Div Prevent Med, Osher Ctr Integrat Med, Boston, MA 02215 USA. [Wayne, Peter M.; Walsh, Jacquelyn N.; Papp, Kathryn V.; Donovan, Nancy J.] Harvard Univ, Sch Med, Boston, MA USA. [Taylor-Piliae, Ruth E.] Univ Arizona, Coll Nursing, Tucson, AZ 85721 USA. [Wells, Rebecca E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27103 USA. [Papp, Kathryn V.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Donovan, Nancy J.] Brigham & Womens Hosp, Dept Psychiat, Ctr Alzheimer Res & Treatment, Boston, MA 02215 USA. [Donovan, Nancy J.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02215 USA. [Yeh, Gloria Y.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Wayne, PM (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA. EM pwayne@partners.org FU National Center for Complementary and Alternative Medicine (NCCAM) [R21 AT005501-01A1]; National Institutes of Health (NIH) FX This publication was made possible by Grant R21 AT005501-01A1 from the National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCCAM or NIH. NR 52 TC 31 Z9 32 U1 6 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2014 VL 62 IS 1 BP 25 EP 39 DI 10.1111/jgs.12611 PG 15 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 292AS UT WOS:000329874600004 PM 24383523 ER PT J AU Dzierzewski, JM Fung, CH Jouldjian, S Alessi, CA Irwin, MR Martin, JL AF Dzierzewski, Joseph M. Fung, Constance H. Jouldjian, Stella Alessi, Cathy A. Irwin, Michael R. Martin, Jennifer L. TI Decrease in Daytime Sleeping Is Associated with Improvement in Cognition After Hospital Discharge in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; cognition; longitudinal change; inpatient hospitalization; older adults ID POST-ACUTE REHABILITATION; ILLNESS RATING-SCALE; NURSING-HOME; DECLINE; POPULATION; VALIDATION; PATTERNS; INSOMNIA; LIFE; CARE AB ObjectivesTo examine the relationship between changes in objectively assessed sleep and global cognitive functioning from inpatient postacute rehabilitation to 6-month follow-up. DesignSecondary analysis of two prospective, longitudinal studies. SettingInpatient rehabilitation units at a Veterans Affairs Medical Center. ParticipantsOlder adults (mean age 73.89.4) undergoing inpatient rehabilitation (n=192). MeasurementsAll participants completed 7 nights and days of ambulatory sleep monitoring using wrist actigraphy (yielding an estimate of nighttime wakefulness and daytime sleep) and the Mini-Mental State Examination (MMSE) during a postacute inpatient rehabilitation stay and 6months after discharge. The 5-item Geriatric Depression Scale, Geriatric Pain Measure, and Cumulative Illness Rating Scale for Geriatrics were completed during inpatient rehabilitation. ResultsGrowth curve modeling (controlling for baseline age, education, sex, body mass index, depression, pain, and comorbidity burden) revealed that individuals whose amount of daytime sleep decreased from inpatient postacute rehabilitation to 6-month follow-up also experienced improvements in MMSE score (=-0.01, t(80=-3.22, P=.002)). Change in nighttime wakefulness was not a significant predictor of change in MMSE score. ConclusionOlder adults whose daytime sleeping decreased after hospital discharge also experienced improvements in cognitive functioning at 6month follow-up. As such, daytime sleep may represent a promising candidate for targeted interventions aimed at promoting cognitive recovery after hospital discharge. C1 [Dzierzewski, Joseph M.; Fung, Constance H.; Jouldjian, Stella; Alessi, Cathy A.; Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Dzierzewski, Joseph M.; Fung, Constance H.; Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Irwin, Michael R.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90024 USA. RP Martin, JL (reprint author), VA Greater Los Angeles Healthcare Syst, 16111 Plummer St 11E, North Hills, CA 91343 USA. EM jennifer.martin@va.gov RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU National Institute on Aging [K23 AG028452]; University of California at Los Angeles (UCLA) Claude D. Pepper Older Americans Independence Center [NIA 5P30 AG028748]; UCLA Cousins Center for Psychoneuroimmunology, VA Health Services Research Development [IIR 04-321-3]; VA Advanced Geriatrics Fellowship Program; American Sleep Medicine Foundation; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center FX This work was supported by the National Institute on Aging (K23 AG028452; PI Martin), University of California at Los Angeles (UCLA) Claude D. Pepper Older Americans Independence Center (NIA 5P30 AG028748, Career Development Award and Pilot Award, Martin; Inflammatory Biology Core, Irwin), UCLA Cousins Center for Psychoneuroimmunology, VA Health Services Research & Development (IIR 04-321-3, Alessi), VA Advanced Geriatrics Fellowship Program (Dzierzewski and Fung), American Sleep Medicine Foundation (Physician Scientist Training Award, Fung), and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. NR 41 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2014 VL 62 IS 1 BP 47 EP 53 DI 10.1111/jgs.12622 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 292AS UT WOS:000329874600006 PM 25093233 ER PT J AU Kim, ES Gustenhoven, E Mescher, MJ Pararas, EEL Smith, KA Spencer, AJ Tandon, V Borenstein, JT Fiering, J AF Kim, Ernest S. Gustenhoven, Erich Mescher, Mark J. Pararas, Erin E. Leary Smith, Kim A. Spencer, Abigail J. Tandon, Vishal Borenstein, Jeffrey T. Fiering, Jason TI A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control SO LAB ON A CHIP LA English DT Article ID HAIR CELL LOSS; INNER-EAR; HEARING-LOSS; GENE-THERAPY; NEUROTROPHIC FACTOR; PLGA NANOPARTICLES; COCHLEA; OTOTOXICITY; DIMENSIONS; GERBILS AB Reciprocating microfluidic drug delivery, as compared to steady or pulsed infusion, has unique features which may be advantageous in many therapeutic applications. We have previously described a device, designed for wearable use in small animal models, that periodically infuses and then withdraws a sub-microliter volume of drug solution to and from the endogenous fluid of the inner ear. This delivery approach results in zero net volume of liquid transfer while enabling mass transport of compounds to the cochlea by means of diffusion and mixing. We report here on an advanced wearable delivery system aimed at further miniaturization and complex dosing protocols. Enhancements to the system include the incorporation of a planar micropump to generate reciprocating flow and a novel drug reservoir that maintains zero net volume delivery and permits programmable modulation of the drug concentration in the infused bolus. The reciprocating pump is fabricated from laminated polymer films and employs a miniature electromagnetic actuator to meet the size and weight requirements of a head-mounted in vivo guinea pig testing system. The reservoir comprises a long microchannel in series with a micropump, connected in parallel with the reciprocating flow network. We characterized in vitro the response and repeatability of the planar pump and compared the results with a lumped element simulation. We also characterized the performance of the reservoir, including repeatability of dosing and range of dose modulation. Acute in vivo experiments were performed in which the reciprocating pump was used to deliver a test compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety and efficacy of the system. These advances are key steps toward realization of an implantable device for long-term therapeutic applications in humans. C1 [Kim, Ernest S.; Gustenhoven, Erich; Mescher, Mark J.; Pararas, Erin E. Leary; Smith, Kim A.; Spencer, Abigail J.; Borenstein, Jeffrey T.; Fiering, Jason] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. [Pararas, Erin E. Leary; Tandon, Vishal] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Kim, ES (reprint author), Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. EM ekim@draper.com RI Tandon, Vishal/F-5699-2016 OI Tandon, Vishal/0000-0002-6618-7846 FU NIH NIDCD [5 R01 DC006848-07] FX We are grateful to William Sewell, Kris Kristiansen, Michael McKenna, and Sharon Kujawa of the Massachusetts Eye and Ear Infirmary for their guidance in establishing device goals and in performing in vivo measurements. This work was made possible by grant number 5 R01 DC006848-07 from NIH NIDCD. NR 49 TC 7 Z9 8 U1 5 U2 38 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 4 BP 710 EP 721 DI 10.1039/c3lc51105g PG 12 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 294KX UT WOS:000330046100011 PM 24302432 ER PT J AU Weber, GF Swirski, FK AF Weber, Georg F. Swirski, Filip K. TI Immunopathogenesis of abdominal sepsis SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Review DE Sepsis; Immune regulation; Translational research ID NONCANONICAL INFLAMMASOME ACTIVATION; POLYMICROBIAL SEPSIS; UNITED-STATES; CELL-DIFFERENTIATION; ENDOTOXIC-SHOCK; INNATE IMMUNITY; ORGAN FAILURE; DR EXPRESSION; IMMUNOSUPPRESSION; MORTALITY AB Sepsis is an unsolved problem worldwide, with a 30-50 % mortality rate. The recent failures of anti-TLR4, recombinant activated protein C, and anti-TNF in clinical trials indicate a need to rethink our current understanding of sepsis's pathophysiology. While the initial immune response is crucial for effective clearance of invading pathogens, an overly exuberant host response to infection can cause septic shock, tissue damage, and death. Profuse inflammation in sepsis is frequently followed by global immunosuppression that increases susceptibility to viral and bacterial infections. Despite the dangers of immune over-response, the immune system's anti-inflammatory activities are likely necessary to reduce the initial over-activation of the immune system. With this review, we want to illuminate the different aspects of immune response to sepsis and provide insight to the ongoing difficulties currently present within sepsis research. Future treatment strategies for sepsis should focus on maintaining balance between pro- and anti-inflammatory immune actions in a timely manner. C1 [Weber, Georg F.] Tech Univ Dresden, Dept Surg, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany. [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA USA. RP Weber, GF (reprint author), Tech Univ Dresden, Dept Surg, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany. EM georg.weber@uniklinikum-dresden.de NR 72 TC 10 Z9 10 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1435-2443 EI 1435-2451 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD JAN PY 2014 VL 399 IS 1 BP 1 EP 9 DI 10.1007/s00423-013-1129-7 PG 9 WC Surgery SC Surgery GA 291MW UT WOS:000329833800001 PM 24121723 ER PT J AU Saglam, M Kantarci, A Dundar, N Hakki, SS AF Saglam, Mehmet Kantarci, Alpdogan Dundar, Niyazi Hakki, Sema S. TI Clinical and biochemical effects of diode laser as an adjunct to nonsurgical treatment of chronic periodontitis: a randomized, controlled clinical trial SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Diode lasers; Chronic periodontitis; Nonsurgical periodontal debridement; Cytokines; Matrix metalloproteinase 1; Matrix metalloproteinase 8 ID GINGIVAL CREVICULAR FLUID; LOW-LEVEL LASER; CARBON-DIOXIDE LASER; TISSUE INHIBITOR; ADULT PERIODONTITIS; IMMUNE-RESPONSES; TERM EVALUATION; MESSENGER-RNA; HOST-RESPONSE; THERAPY AB The aim of this randomized, parallel, controlled clinical trial was to examine the clinical and biochemical efficacy of diode laser as an adjunct to scaling and root planing (SRP). Thirty chronic periodontitis patients were randomly assigned into two groups to receive SRP alone (control) or SRP followed by diode laser (test). Plaque index, gingival index, bleeding on probing, probing depth, and clinical attachment level were measured at baseline and at 1, 3, and 6 months after treatment. The gingival crevicular fluid levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) were analyzed by enzyme-linked immunosorbent assay. Test group showed significantly a better outcome compared to the control group in full-mouth clinical parameters. MMP-1, MMP-8, and TIMP-1 showed significant differences between groups after treatment compared to baseline (p < 0.05). The total amount of IL-1 beta, IL-6, MMP-1, MMP-8, and TIMP-1 decreased (p < 0.05) and IL-8 increased after treatment in both test and control groups (p < 0.05). Diode laser provided significant improvements in clinical parameters and MMP-8 was significantly impacted by the adjunctive laser treatment at first month providing an insight to how lasers can enhance the outcomes of the nonsurgical periodontal therapy. C1 [Saglam, Mehmet] Izmir Katip Celebi Univ, Dept Periodontol, Fac Dent, Izmir, Turkey. [Kantarci, Alpdogan] Forsyth Inst, Boston, MA USA. [Dundar, Niyazi] Selcuk Univ, Fac Dent, Res Ctr, Konya, Turkey. [Saglam, Mehmet; Hakki, Sema S.] Selcuk Univ, Dept Periodontol, Fac Dent, Konya, Turkey. RP Saglam, M (reprint author), Izmir Katip Celebi Univ, Dept Periodontol, Fac Dent, Izmir, Turkey. EM dtmehmetsaglam@gmail.com FU Scientific Research Coordination Office of Selcuk University, Konya, Turkey; The Scientific and Technological Research Council of Turkey [TUBITAK/SBAG-110S502] FX This study was supported by the Scientific Research Coordination Office of Selcuk University, Konya, Turkey and The Scientific and Technological Research Council of Turkey (TUBITAK/SBAG-110S502). The authors report no conflicts of interest related to this study. NR 72 TC 22 Z9 23 U1 0 U2 9 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 EI 1435-604X J9 LASER MED SCI JI Lasers Med. Sci. PD JAN PY 2014 VL 29 IS 1 BP 37 EP 46 DI 10.1007/s10103-012-1230-0 PG 10 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA 291NA UT WOS:000329834200005 PM 23161345 ER PT J AU Gupta, A Dai, TH Hamblin, MR AF Gupta, Asheesh Dai, Tianhong Hamblin, Michael R. TI Effect of red and near-infrared wavelengths on low-level laser (light) therapy-induced healing of partial-thickness dermal abrasion in mice SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Cytokeratin-14; Low-level laser (light) therapy; Near-infrared; Partial-thickness abrasion; Photobiomodulation; Proliferating cell nuclear antigen (PCNA) ID CYTOCHROME-C-OXIDASE; HELIUM-NEON LASER; GENE-EXPRESSION; IR RADIATION; HE-NE; IRRADIATION; PHOTOBIOMODULATION; PROLIFERATION; PHOTOTHERAPY; FIBROBLASTS AB Low-level laser (light) therapy (LLLT) promotes wound healing, reduces pain and inflammation, and prevents tissue death. Studies have explored the effects of various radiant exposures on the effect of LLLT; however, studies of wavelength dependency in in vivo models are less common. In the present study, the healing effects of LLLT mediated by different wavelengths of light in the red and near-infrared (NIR) wavelength regions (635, 730, 810, and 980 nm) delivered at constant fluence (4 J/cm(2)) and fluence rate (10 mW/cm(2)) were evaluated in a mouse model of partial-thickness dermal abrasion. Wavelengths of 635 and 810 nm were found to be effective in promoting the healing of dermal abrasions. However, treatment using 730- and 980-nm wavelengths showed no sign of stimulated healing. Healing was maximally augmented in mice treated with an 810-nm wavelength, as evidenced by significant wound area reduction (p < 0.05), enhanced collagen accumulation, and complete re-epithelialization as compared to other wavelengths and non-illuminated controls. Significant acceleration of re-epithelialization and cellular proliferation revealed by immunofluorescence staining for cytokeratin-14 and proliferating cell nuclear antigen (p < 0.05) was evident in the 810-nm wavelength compared with other groups. Photobiomodulation mediated by red (635 nm) and NIR (810 nm) light suggests that the biological response of the wound tissue depends on the wavelength employed. The effectiveness of 810-nm wavelength agrees with previous publications and, together with the partial effectiveness of 635 nm and the ineffectiveness of 730 and 980 nm wavelengths, can be explained by the absorption spectrum of cytochrome c oxidase, the candidate mitochondrial chromophore in LLLT. C1 [Gupta, Asheesh; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gupta, Asheesh; Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Gupta, Asheesh] Def Inst Physiol & Allied Sci, Delhi 110054, India. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875]; BOYSCAST; Airlift Research Foundation [109421] FX This work was funded by the US NIH (R01AI050875). Asheesh Gupta was supported by BOYSCAST Fellowship 2010-11 (Department of Science and Technology, Govt. of India). Tianhong Dai was supported by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). We would like to acknowledge and deeply thank Jie Zhao, PhD, for her expertise and guidance with confocal microscopy and Peggy Sherwood and Julie LaGraves for their technical help with histology. NR 31 TC 23 Z9 23 U1 2 U2 18 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 EI 1435-604X J9 LASER MED SCI JI Lasers Med. Sci. PD JAN PY 2014 VL 29 IS 1 BP 257 EP 265 DI 10.1007/s10103-013-1319-0 PG 9 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA 291NA UT WOS:000329834200034 PM 23619627 ER PT J AU Jalian, HR Avram, MM Stankiewicz, KJ Shofner, JD Tannous, Z AF Jalian, H. Ray Avram, Mathew M. Stankiewicz, Kelly J. Shofner, Joshua D. Tannous, Zeina TI Combined 585nm Pulsed-Dye and 1,064nm Nd:YAG Lasers for the Treatment of Basal Cell Carcinoma SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE basal cell carcinoma; pulsed-dye laser; Nd:YAG ID MICROSCOPY; RADIATION AB Background and ObjectiveBasal cell carcinomas (BCCs) have supporting vasculature that serves as a target for vascular selective lasers. The objective of this study was to determine the effect of repeated treatment with a combined 585nm pulsed dye laser (PDL) and 1,064nm Neodymium Yttrium Aluminum Garnet (Nd:YAG) laser on BCCs of superficial and nodular subtypes of varying diameters. Study Design/Materials and MethodsTen subjects with 13 biopsy-proven BCCs received four combined PDL and Nd:YAG at treatments 2-4 week intervals. None of the BCCs met the criteria for Mohs micrographic surgery. The tumor and 4mm of peripheral skin were treated using standardized parameters delivered with a 7mm spot with 10% overlap. The treated area was excised and evaluated histologically for residual tumor. The primary study endpoint was histologic clearance of tumor. The secondary study endpoint was blinded investigator assessment of clinical endpoint and adverse effects. ResultsApproximately half of all tumors showed a complete response to four combined PDL and Nd:YAG treatments (n=7/12, 58%). When stratified by size, 75% of all tumors <1cm in diameter (n=6/8) showed complete response. Tumor histologic types among the complete responders included superficial and nodular BCCs. All subjects with incompletely responding BCCs were on various forms of anticoagulation, which we hypothesize, may inhibit laser-mediated thrombosis necessary for the clinical effect. Blinded investigator assessment suggests that biopsy related erythema improves with subsequent laser treatments. ConclusionsCombined PDL and Nd:YAG laser is an effective means of reducing tumor burden in patients with BCC and may be a promising, emerging alternative therapy. Factors influencing treatment response includes the concomitant use of anticoagulation. Further studies are needed to investigate and optimize the utility of this treatment protocol. Lasers Surg. Med. 46:1-7, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Jalian, H. Ray] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90025 USA. [Jalian, H. Ray; Avram, Mathew M.; Stankiewicz, Kelly J.; Shofner, Joshua D.; Tannous, Zeina] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Jalian, H. Ray; Avram, Mathew M.; Stankiewicz, Kelly J.; Shofner, Joshua D.; Tannous, Zeina] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tannous, Zeina] Lebanese Amer Univ, Dept Dermatol, Beirut, Lebanon. RP Jalian, HR (reprint author), 2020 Santa Monica Blvd,Suite 570, Santa Monica, CA 90404 USA. EM hjalian@partners.org FU Cynosure, Inc. FX Contract grant sponsor: Cynosure, Inc. NR 19 TC 4 Z9 4 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD JAN PY 2014 VL 46 IS 1 BP 1 EP 7 DI 10.1002/lsm.22201 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 291UX UT WOS:000329857400001 PM 24272664 ER PT S AU Sullivan, RJ Atkins, MB AF Sullivan, Ryan J. Atkins, Michael B. BE Thurin, M Marincola, FM TI Emerging Clinical Issues in Melanoma in the Molecularly Targeted Era SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE BRAF; NRAS; Predictive biomarkers; Patient selection; Treatment sequencing ID RECOMBINANT INTERLEUKIN-2 THERAPY; INHIBITOR AZD6244 ARRY-142886; STAGE IV MELANOMA; PHASE-III TRIAL; METASTATIC MELANOMA; ADJUVANT THERAPY; OPEN-LABEL; MONOCLONAL-ANTIBODY; IMATINIB MESYLATE; IMPROVED SURVIVAL AB The standard of care of patients with malignant melanoma is dramatically changing, hallmarked by the approval of three new agents for the treatment of malignant melanoma in 2011. In this changing therapeutic landscape, several clinical issues are emerging which will best be addressed through the application of advances in molecular analytics, diagnostics, and therapeutics. It is expected that dedicated and coordinated efforts in basic, translational, and clinical will be responsible for the next major breakthroughs in the care of patients with this dreaded disease. In this chapter, five critical, emerging clinical issues are presented with descriptions of approaches that might be expected to help solve these challenges to optimal patient care. C1 [Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. NR 81 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 11 EP 26 DI 10.1007/978-1-62703-727-3_2 D2 10.1007/978-1-62703-727-3 PG 16 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000003 PM 24258971 ER PT S AU Panka, DJ Mier, JW Sullivan, RJ AF Panka, David J. Mier, James W. Sullivan, Ryan J. BE Thurin, M Marincola, FM TI Assaying for BRAF V600E in Tissue and Blood in Melanoma SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE BRAF(V600E); Biomarker; Target; Melanoma test; TspR1restriction digestion; Vemurafenib; Dabrafenib; Trametanib ID PAPILLARY THYROID-CARCINOMA; RAF INHIBITOR RESISTANCE; REAL-TIME PCR; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; MUTATION ANALYSIS; COLON-CANCER; BRAF(V600E); CELLS; AMPLIFICATION AB The Braf(V600E) mutation has been detected in patients with metastatic melanoma, colon, thyroid, and other cancers. Studies suggested that tumors with this mutation are especially sensitive to BRAF inhibitors-hence the need to reliably determine the BRAF status of tumor specimens. The present technologies used to screen for this mutation fail to address the problems associated with infiltrating stromal and immune cells bearing wildtype BRAF alleles and thus may fail to detect the presence of mutant BRAF(V600E) tumors. We have developed a rapid, inexpensive method of BRAF analysis that reduces the contamination of wild-type BRAF sequences from tumor biopsies. The protocol involves a series of PCR amplifications and restriction digestions that take advantage of unique features of both wild-type and mutant BRAF RNA at codon 600. Using this protocol, mutant BRAF can be detected in RNA from mixed populations with as few as 0.1 % BRAF(V600E) mutant containing cells. C1 [Panka, David J.; Mier, James W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA. RP Panka, DJ (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 48 TC 3 Z9 4 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 117 EP 136 DI 10.1007/978-1-62703-727-3_8 D2 10.1007/978-1-62703-727-3 PG 20 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000009 PM 24258977 ER PT S AU Levine, D Fisher, DE AF Levine, Danielle Fisher, David E. BE Thurin, M Marincola, FM TI Current Status of Diagnostic and Prognostic Markers in Melanoma SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Melanoma; Biomarker; Prognosis; Epigenetic; Proteomic ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; MESSENGER-RNA EXPRESSION; CANCER STAGE-IV; FOLLOW-UP; TRANSCRIPTIONAL REGULATION; LACTATE-DEHYDROGENASE; METASTATIC MELANOMA; DOWN-REGULATION; SERUM-LEVELS AB Melanoma is the most life-threatening common form of skin cancer. While most cutaneous melanomas are cured by surgical resection, a minority will relapse locally, regionally, or distantly. Biomarkers have represented a focal point for research aimed at improving diagnostic accuracy as well as providing prognostic information that may help to guide therapeutic decisions. While systemic melanoma therapies were of extremely limited utility for patients with advanced disease in the past, two drugs have been approved the FDA within the past several years, and it is possible that they may provide even greater impact if employed earlier in the disease process. To optimally employ these therapies, prognostic biomarkers may offer significant value. This article reviews methodologies for both discovery and routine testing of melanoma biomarkers. It also focuses on specific commonly used markers, as well as approaches to studying their applications to specific clinical settings. As the armamentarium of melanoma drugs grows, it is hoped that specific biomarkers will aid in guiding the use of these agents for patients in the clinic. C1 [Levine, Danielle; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Levine, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 89 TC 5 Z9 5 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 177 EP 197 DI 10.1007/978-1-62703-727-3_11 D2 10.1007/978-1-62703-727-3 PG 21 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000012 PM 24258980 ER PT S AU Marzuka-Alcala, A Gabree, MJ Tsao, HS AF Marzuka-Alcala, Alexander Gabree, Michele Jacobs Tsao, Hensin BE Thurin, M Marincola, FM TI Melanoma Susceptibility Genes and Risk Assessment SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Familial melanoma; Hereditary melanoma; CDKN2A; p16INK4a; P14ARF; MC1R; MITF; BAP1; Genome-wide association studies; Cancer risk assessment; MelaPRO; COMMON syndrome ID GENOME-WIDE ASSOCIATION; CDKN2A CARRIER PROBABILITY; CELL-CYCLE INHIBITION; GERM-LINE MUTATIONS; CUTANEOUS MELANOMA; FAMILIAL MELANOMA; MALIGNANT MESOTHELIOMA; PANCREATIC-CANCER; IDENTIFIES 3; SKIN-CANCER AB Familial melanoma accounts for approximately a tenth of all melanoma cases. The most commonly known melanoma susceptibility gene is the highly penetrant CDKN2A (p16INK4a) locus, which is transmitted in an autosomal dominant fashion and accounts for approximately 20-50 % of familial melanoma cases. Mutated p16INK4a shows impaired capacity to inhibit the cyclin D1-CDK4 complex, allowing for unchecked cell cycle progression. Mutations in the second protein coded by CDKN2A, p14ARF, are much less common and result in proteasomal degradation of p53 with subsequent accumulation of DNA damage as the cell progresses through the cell cycle without a functional p53-mediated DNA damage response. Mutations in CDK4 that impair the inhibitory interaction with p16INK4a also increase melanoma risk but these mutations are extremely rare. Genes of the melanin biosynthetic pathway, including MC1R and MITF, have also been implicated in melanomagenesis. MC1R variants were traditionally thought to increase risk for melanoma secondary to intensified UV-mediated DNA damage in the setting of absent photoprotective eumelanin. Accumulation of pheomelanin, which appears to have a carcinogenic effect regardless of UV exposure, may be a more likely mechanism. Impaired SUMOylation of the E318K variant of MITF results in increased transcription of genes that confer melanocytes with a pro-malignant phenotype. Mutations in the tumor suppressor BAP1 enhance the metastatic potential of uveal melanoma and predispose to cutaneous/ocular melanoma, atypical melanocytic tumors, and other internal malignancies (COMMON syndrome). Genome-wide association studies have identified numerous low-risk alleles. Although several melanoma susceptibility genes have been identified, risk assessment tools have been developed only for the most common gene implicated with hereditary melanoma, CDKN2A. MelaPRO, a validated model that relies on Mendelian inheritance and Bayesian probability theories, estimates carrier probability for CDKN2A and future risk of melanoma taking into account a patient's family and past medical history of melanoma. Genetic testing for CDKN2A mutations is currently available but the Melanoma Genetics Consortium recommends offering such testing to patients only in the context of research protocols because clinical utility is uncertain. C1 [Marzuka-Alcala, Alexander] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Gabree, Michele Jacobs] Massachusetts Gen Hosp, Ctr Canc Risk Assessment, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. RP Marzuka-Alcala, A (reprint author), Yale Univ, Sch Med, New Haven, CT 06520 USA. FU NCI NIH HHS [K24 CA149202] NR 56 TC 20 Z9 20 U1 0 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 381 EP 393 DI 10.1007/978-1-62703-727-3_20 D2 10.1007/978-1-62703-727-3 PG 13 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000021 PM 24258989 ER PT S AU Rashid, AB Grossniklaus, HE AF Rashid, Alia B. Grossniklaus, Hans E. BE Thurin, M Marincola, FM TI Clinical, Pathologic, and Imaging Features and Biological Markers of Uveal Melanoma SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Uveal melanoma; Clinical features; Histopathology; Biological markers; Imaging; Prognosis ID COLLABORATIVE OCULAR MELANOMA; CILIARY BODY MELANOMAS; CHOROIDAL MALIGNANT-MELANOMA; LIVER-FUNCTION TESTS; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; SOLITARY PULMONARY METASTASIS; COMS RANDOMIZED-TRIAL; 10 LARGEST NUCLEOLI; LONG-TERM SURVIVAL; PROGNOSTIC-FACTORS AB Uveal melanoma has unique clinical and pathologic features including virtually exclusive metastasis to the liver in high-risk cases. In this chapter, the clinical findings in uveal melanoma and diagnostic methods including imaging tests and serum markers are described. Additionally, the histopathologic features including the modified Callender classification and immunohistochemical findings of uveal melanoma are described. C1 [Rashid, Alia B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA 02115 USA. [Grossniklaus, Hans E.] Emory Univ, Sch Med, Atlanta, GA USA. RP Rashid, AB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA 02115 USA. NR 143 TC 7 Z9 8 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 397 EP 425 DI 10.1007/978-1-62703-727-3_21 D2 10.1007/978-1-62703-727-3 PG 29 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000022 PM 24258990 ER PT S AU Wang, YY Sabbatino, F Wang, XH Ferrone, S AF Wang, Yangyang Sabbatino, Francesco Wang, Xinhui Ferrone, Soldano BE Thurin, M Marincola, FM TI Detection of Chondroitin Sulfate Proteoglycan 4 (CSPG4) in Melanoma SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE CSPG4; Melanoma; RT-PCR; IHC staining ID ANTIGEN HMW-MAA; ANTIIDIOTYPIC MONOCLONAL-ANTIBODIES; CELL-SURFACE; BREAST-CANCER; MIMICRY; IMMUNOGENICITY; IMMUNOTHERAPY; HETEROGENEITY; IMMUNITY; TARGET AB The tumor antigen chondroitin sulfate proteoglycan 4 (CSPG4) appears to be a useful biomarker to identify melanoma cells and an attractive target to apply antibody-based immunotherapy for the treatment of melanoma. Here we described the reverse transcription-polymerase chain reaction (RT-PCR) method and the immunohistochemical (IHC) staining method to detect the expression of CSPG4 in melanoma cells and tissues. C1 [Wang, Yangyang; Sabbatino, Francesco; Wang, Xinhui] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg & Orthopaed Surg, Boston, MA USA. RP Wang, YY (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Sabbatino, Francesco/F-4992-2014 OI Sabbatino, Francesco/0000-0001-6431-8278 FU NCI NIH HHS [R01 CA110249, R01-1CA138188] NR 25 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 523 EP 535 DI 10.1007/978-1-62703-727-3_28 D2 10.1007/978-1-62703-727-3 PG 13 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000029 PM 24258997 ER PT S AU Castellanos-Rizaldos, E Milbury, CA Guha, M Makrigiorgos, GM AF Castellanos-Rizaldos, Elena Milbury, Coren A. Guha, Minakshi Makrigiorgos, G. Mike BE Thurin, M Marincola, FM TI COLD-PCR Enriches Low-Level Variant DNA Sequences and Increases the Sensitivity of Genetic Testing SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Coamplification at lower denaturation temperature (COLD-PCR); Mutation detection; Low-level mutations; Cancer; Diagnosis; Prognosis; Therapy targets ID SINGLE-NUCLEOTIDE POLYMORPHISMS; KRAS MUTATION DETECTION; MELTING ANALYSIS; LUNG-CANCER; POOLED DNA; PLASMA; TISSUE; ASSAYS AB Detection of low-level mutations is important for cancer biomarker and therapy targets discovery, but reliable detection remains a technical challenge. The newly developed method of CO-amplification at Lower Denaturation temperature PCR (COLD-PCR) helps to circumvent this issue. This PCR-based technology preferentially enriches minor known or unknown variants present in samples with a high background of wild type DNA which often hampers the accurate identification of these minority alleles. This is a simple process that consists of lowering the temperature at the denaturation step during the PCR-cycling protocol (critical denaturation temperature, T c) and inducing DNA heteroduplexing during an intermediate step. COLD-PCR in its simplest forms does not need additional reagents or specific instrumentation and thus, can easily replace conventional PCR and at the same time improve the mutation detection sensitivity limit of downstream technologies. COLD-PCR can be applied in two basic formats: fast-COLD-PCR that can enrich T m-reducing mutations and full-COLD-PCR that can enrich all mutations, though it requires an intermediate cross-hybridization step that lengthens the thermocycling program. An improved version of full-COLD-PCR (improved and complete enrichment, ice-COLD-PCR) has also been described. Finally, most recently, we developed yet another form of COLD-PCR, temperature-tolerant-COLD-PCR, which gradually increases the denaturation temperature during the COLD-PCR reaction, enriching diverse targets using a single cycling program. This report describes practical considerations for application of fast-, full-, ice-, and temperature-tolerant-COLD-PCR for enrichment of mutations prior to downstream screening. C1 [Castellanos-Rizaldos, Elena; Guha, Minakshi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA 02115 USA. [Milbury, Coren A.; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Guha, Minakshi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Phys & Biophys,Dept Radiat Oncol, Boston, MA 02115 USA. RP Castellanos-Rizaldos, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-151164, CA-111994] NR 29 TC 2 Z9 3 U1 2 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-726-6; 978-1-62703-727-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1102 BP 623 EP 639 DI 10.1007/978-1-62703-727-3_33 D2 10.1007/978-1-62703-727-3 PG 17 WC Oncology SC Oncology GA BJM68 UT WOS:000329172000034 PM 24259002 ER PT J AU Hurd, YL Michaelides, M Miller, ML Jutras-Aswad, D AF Hurd, Yasmin L. Michaelides, Michael Miller, Michael L. Jutras-Aswad, Didier TI Trajectory of adolescent cannabis use on addiction vulnerability SO NEUROPHARMACOLOGY LA English DT Review DE Marijuana; Cannabinoid; Opioid neuropeptide; Nucleus accumbens; Prefrontal cortex ID RECEPTOR MESSENGER-RNA; ILLICIT DRUG-USE; PROENKEPHALIN GENE-EXPRESSION; BRAIN GLUCOSE-METABOLISM; POPULATION-BASED SAMPLE; MARIJUANA USE; RAT-BRAIN; ENVIRONMENTAL-INFLUENCES; DOPAMINE-D-2 RECEPTORS; GATEWAY HYPOTHESIS AB The adolescent brain is a period of dynamic development making it vulnerable to environmental factors such as drug exposure. Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data. We provide an overview of the endocannabinoid system in relation to adolescent cannabis exposure and provide insights regarding factors such as genetics and behavioral traits that confer risk for subsequent addiction. While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hurd, Yasmin L.; Michaelides, Michael; Miller, Michael L.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Hurd, Yasmin L.; Michaelides, Michael; Miller, Michael L.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Hurd, Yasmin L.] James J Peters Vet Adm, Bronx, NY USA. [Jutras-Aswad, Didier] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Jutras-Aswad, Didier] Ctr Hosp Univ Montreal, CRCHUM, Montreal, PQ, Canada. RP Hurd, YL (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM Yasmin.hurd@mssm.edu OI Miller, Michael/0000-0002-6350-5706 FU NIDA [DA030359, DA023214] FX This work was funded by NIDA DA030359 and DA023214. NR 124 TC 24 Z9 25 U1 9 U2 51 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2014 VL 76 SI SI BP 416 EP 424 DI 10.1016/j.neuropharm.2013.07.028 PN B PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 294YK UT WOS:000330083600022 PM 23954491 ER PT J AU Tirumani, SH Shanbhogue, AKP Vikram, R Prasad, SR Menias, CO AF Tirumani, Sree Harsha Shanbhogue, Alampady Krishna Prasad Vikram, Raghunandan Prasad, Srinivasa R. Menias, Christine O. TI Imaging of the Porta Hepatis: Spectrum of Disease SO RADIOGRAPHICS LA English DT Article ID ORTHOTOPIC LIVER-TRANSPLANTATION; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER; VISCERAL ARTERY ANEURYSMS; VEIN THROMBOSIS; ENDOVASCULAR THERAPY; BILIARY STRICTURES; MR CHOLANGIOPANCREATOGRAPHY; HEPATOCELLULAR-CARCINOMA; HILAR CHOLANGIOCARCINOMA; AUTOIMMUNE PANCREATITIS AB A wide array of pathologic conditions can arise within the porta hepatis, which encompasses the portal triad (the main portal vein, common hepatic artery, and common bile ducts), lymphatics, nerves, and connective tissue. Major vascular diseases of the portal triad include thrombosis, stenosis, and aneurysm. Portal vein thrombosis can complicate liver cirrhosis and hepatocellular carcinoma and has important therapeutic implications. Hepatic artery thrombosis and stenosis require immediate attention to reduce graft loss in liver transplant recipients. Congenital (eg, choledochal cyst) and acquired (benign and malignant) diseases of the biliary system can manifest as mass lesions in the porta hepatis. Lymphadenopathy can arise from neoplastic and nonneoplastic entities. Uncommon causes of mass lesions arise from nerves (eg, neurofibroma, neurofibrosarcoma) and connective tissue (sarcomas) and are rare. The hepatoduodenal ligament is a peritoneal reflection at the porta hepatis and is an important route for the spread of pancreatic and gastrointestinal cancers. Imaging plays a major role in diagnosis and enables appropriate management. Ultrasonography accurately demonstrates anatomic variations and pathologic conditions and is the initial modality of choice for detection of vascular and biliary lesions. Multidetector computed tomography and magnetic resonance imaging allow characterization and differentiation of various masses in the porta hepatis. Imaging-guided interventions, including embolization and stent placement, also play a key role in disease management. (C)RSNA, 2014 C1 [Tirumani, Sree Harsha] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Tirumani, Sree Harsha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Shanbhogue, Alampady Krishna Prasad] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Vikram, Raghunandan; Prasad, Srinivasa R.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Menias, Christine O.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. RP Shanbhogue, AKP (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 16th St & 1st Ave, New York, NY 10003 USA. EM shanbhoguekp@gmail.com NR 77 TC 12 Z9 13 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2014 VL 34 IS 1 BP 73 EP 92 DI 10.1148/rg.341125190 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292QP UT WOS:000329917500013 PM 24428283 ER PT J AU Moshiri, M Zaidi, SF Robinson, TJ Bhargava, P Siebert, JR Dubinsky, TJ Katz, DS AF Moshiri, Mariam Zaidi, Sadaf F. Robinson, Tracy J. Bhargava, Puneet Siebert, Joseph R. Dubinsky, Theodore J. Katz, Douglas S. TI Comprehensive Imaging Review of Abnormalities of the Umbilical Cord SO RADIOGRAPHICS LA English DT Review ID PRENATAL ULTRASOUND DIAGNOSIS; OF-THE-LITERATURE; NUCHAL CORD; VEIN VARIX; COILING INDEX; RISK-FACTORS; SONOGRAPHIC EVALUATION; CLINICAL IMPORTANCE; DOPPLER SONOGRAPHY; PERINATAL OUTCOMES AB A complete fetal ultrasonographic (US) study includes assessment of the umbilical cord for possible abnormalities. Knowledge of the normal appearance of the umbilical cord is necessary for the radiologist to correctly diagnose pathologic conditions. Umbilical cord abnormalities can be related to cord coiling, length, and thickness; the placental insertion site; in utero distortion; vascular abnormalities; and primary tumors or masses. These conditions may be associated with other fetal anomalies and aneuploidies, and their discovery should prompt a thorough fetal US examination. Further workup and planning for a safe fetal delivery may include fetal echocardiography and karyotype analysis. Doppler US is a critical tool for assessment and diagnosis of vascular cord abnormalities. US also can be used for follow-up serial imaging evaluation of conditions that could result in fetal demise. Recent studies suggest that three- or four-dimensional Doppler US of the fetal umbilical cord and abdominal vasculature allows more accurate diagnosis of vascular abnormalities. Doppler US also is invaluable in assessment of fetal growth restriction since hemodynamic changes in the placenta or fetus would appear as a spectral pattern of increased resistance to forward flow in the fetal umbilical artery. Early detection of umbilical cord abnormalities and close follow-up can reduce the risk of morbidity and mortality and assist in decision making. (C)RSNA, 2014 C1 [Moshiri, Mariam; Zaidi, Sadaf F.; Robinson, Tracy J.; Bhargava, Puneet; Dubinsky, Theodore J.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Siebert, Joseph R.] Seattle Childrens Hosp, Dept Labs, Seattle, WA USA. [Katz, Douglas S.] Winthrop Univ Hosp, Dept Radiol, Mineola, NY 11501 USA. RP Moshiri, M (reprint author), Univ Washington, Sch Med, Dept Radiol, 1959 NE Pacific St, Seattle, WA 98195 USA. EM moshiri@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 70 TC 6 Z9 6 U1 0 U2 12 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2014 VL 34 IS 1 BP 179 EP 196 DI 10.1148/rg.341125127 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292QP UT WOS:000329917500020 PM 24428290 ER PT J AU Yeh, ED Georgian-Smith, D Raza, S Bussolari, L Pawlisz-Hoff, J Birdwell, RL AF Yeh, Eren D. Georgian-Smith, Dianne Raza, Sughra Bussolari, Lisa Pawlisz-Hoff, Jacqueline Birdwell, Robyn L. TI Positioning in Breast MR Imaging to Optimize Image Quality SO RADIOGRAPHICS LA English DT Article ID ARTIFACTS AB Improper positioning of the breasts in a dedicated breast coil causes inhomogeneous fat saturation as well as other artifacts that decrease the sensitivity of breast magnetic resonance imaging. Improper positioning can create artifacts that can obscure a malignancy or cause it to be missed. Goals of proper positioning include imaging the maximum area of breast tissue, minimizing skin folds, and achieving homogeneous fat suppression and nondeformed breast parenchyma. Review of prior images gives the technologist an impression of what the positioning and imaging challenges may be in each patient before the patient enters the imaging unit. Checking the triplane localizer images and repositioning as necessary before any diagnostic or interventional imaging is key. Using a fat saturation pad, changing the arm position, or "rolling" the patient may be considered in difficult cases. Padding to support the patient in an oblique position, using angled sponges to increase breast compression thickness, and raising the grid to access posterior lesions may be helpful in targeting difficult-to-access lesions for biopsy. Using the presented positioning techniques and suggestions, in addition to strict attention to detail before imaging, will improve image quality, decrease imaging time and suboptimal images, and limit the need for repeat imaging studies. (C) RSNA, 2014 C1 [Yeh, Eren D.; Georgian-Smith, Dianne; Raza, Sughra; Bussolari, Lisa; Birdwell, Robyn L.] Brigham & Womens Hosp, Div Breast Imaging, Dept Radiol, Boston, MA 02115 USA. [Yeh, Eren D.; Georgian-Smith, Dianne; Raza, Sughra; Bussolari, Lisa; Birdwell, Robyn L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Pawlisz-Hoff, Jacqueline] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Yeh, ED (reprint author), Brigham & Womens Hosp, Div Breast Imaging, Dept Radiol, 75 Francis St,RA Bldg,RA 014, Boston, MA 02115 USA. EM eyeh@partners.org NR 6 TC 3 Z9 4 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2014 VL 34 IS 1 BP E1 EP E17 DI 10.1148/rg.341125193 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292QP UT WOS:000329917500005 PM 24428300 ER PT J AU Dang, PA Freer, PE Humphrey, KL Halpern, EF Rafferty, EA AF Dang, Pragya A. Freer, Phoebe E. Humphrey, Kathryn L. Halpern, Elkan F. Rafferty, Elizabeth A. TI Addition of Tomosynthesis to Conventional Digital Mammography: Effect on Image Interpretation Time of Screening Examinations SO RADIOLOGY LA English DT Article ID BREAST TOMOSYNTHESIS; PERFORMANCE; POPULATION; OBSERVER; PROGRAM AB Purpose: To determine the effect of implementing a screening tomosynthesis program on real-world clinical performance by quantifying differences between interpretation times for conventional screening mammography and combined tomosynthesis and mammography for multiple participating radiologists with a wide range of experience in a large academic center. Materials and Methods: In this HIPAA-compliant, institutional review board-approved study, 10 radiologists prospectively read images from screening digital mammography or screening combined tomosynthesis and mammography examinations for 1-hour-long uninterrupted sessions. Images from 3665 examinations (1502 combined and 2163 digital mammography) from July 2012 to January 2013 were interpreted in at least five sessions per radiologist per modality. The number of cases reported during each session was recorded for each reader. The experience level for each radiologist was also correlated to the average number of cases reported per hour. Analysis of variance was used to assess the number of studies interpreted per hour. A linear regression model was used to evaluate correlation between breast imaging experience and time taken to interpret images from both modalities. Results: The mean number of studies interpreted in hour was 23.8 +/- 0.55 (standard deviation) (range, 14.4-40.4) for combined tomosynthesis and mammography and 34.0 +/- 0.55 (range, 20.4-54.3) for digital mammography alone. A mean of 10.2 fewer studies were interpreted per hour during combined tomosynthesis and mammography compared with digital mammography sessions (P < .0001). The mean interpretation time was 2.8 minutes +/- 0.9 (range, 1.5-4.2 minutes) for combined tomosynthesis and mammography and 1.9 minutes +/- 0.6 (range, 1.1-3.0) for digital mammography; interpretation time with combined tomosynthesis and mammography was 0.9 minute longer (47% longer) compared with digital mammography alone (P < .0001). With the increase in years of breast imaging experience, the overall additional time required to read images from combined tomosynthesis and mammography examinations decreased (R-2 = 0.52, P = .03). Conclusion: Addition of tomosynthesis to mammography results in increased time to interpret images from screening examinations compared with time to interpret images from conventional digital mammography alone. (C) RSNA, 2014 C1 [Dang, Pragya A.; Freer, Phoebe E.; Humphrey, Kathryn L.; Halpern, Elkan F.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Dang, PA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 216, Boston, MA 02114 USA. EM pdang1@partners.org OI Freer, Phoebe/0000-0001-6886-7100 NR 12 TC 17 Z9 18 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2014 VL 270 IS 1 BP 49 EP 56 DI 10.1148/radiol.13130765 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292QC UT WOS:000329916100007 PM 24354377 ER PT J AU Hunter, GJ Ginat, DT Kelly, HR Halpern, EF Hamberg, LM AF Hunter, George J. Ginat, Daniel T. Kelly, Hillary R. Halpern, Elkan F. Hamberg, Leena M. TI Discriminating Parathyroid Adenoma from Local Mimics by Using Inherent Tissue Attenuation and Vascular Information Obtained with Four-Dimensional CT: Formulation of a Multinomial Logistic Regression Model SO RADIOLOGY LA English DT Article ID OPERATING CHARACTERISTIC CURVES; PRIMARY HYPERPARATHYROIDISM; COMPUTED-TOMOGRAPHY; DIRECTED PARATHYROIDECTOMY; LOCALIZATION; ACCURACY AB Purpose: To identify a set of parameters, which are based on tissue enhancement and native iodine content obtained from a standardized triple-phase four-dimensional (4D) computed tomographic (CT) scan, that define a multinomial logistic regression model that discriminates between parathyroid adenoma (PTA) and thyroid nodules or lymph nodes. Materials and Methods: Informed consent was waived by the institutional review board for this retrospective HIPAA-compliant study. Electronic medical records were reviewed for 102 patients with hyperparathyroidism who underwent triple-phase 4D CT and parathyroid surgery resulting in pathologically proved removal of adenoma from July 2010 through December 2011. Hounsfield units were measured in PTA, thyroid, lymph nodes, and aorta and were used to determine seven parameters characterizing tissue contrast enhancement. These were used as covariates in 10 multinomial logistic regression models. Three models with one covariate, four models with two covariates, and three models with three covariates were investigated. Receiver operating characteristic (ROC) analysis was performed to determine how well each model discriminated between adenoma and nonadenomatous tissues. Statistical differences between the areas under the ROC curves (AUCs) for each model pair were calculated, as well as sensitivity, specificity, accuracy, negative predictive value, and positive predictive value. Results: A total of 120 lesions were found; 112 (93.3%) lesions were weighed, and mean and median weights were 589 and 335 mg, respectively. The three-covariate models were significantly identical (P > .65), with largest AUC of 0.9913 +/- 0.0037 (standard error), accuracy of 96.9%, and sensitivity, specificity, negative predictive value, and positive predictive value of 94.3%, 98.3%, 97.1%, and 96.7%, respectively. The one- and two-covariate models were significantly less accurate (P < .043). Conclusion: A three-covariate multinomial logistic model derived from a triple-phase 4D CT scan can accurately provide the probability that tissue is PTA and performs significantly better than models using one or two covariates. (C) RSNA, 2013 C1 [Hunter, George J.; Ginat, Daniel T.; Kelly, Hillary R.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hamberg, Leena M.] Brigham & Womens Hosp, Dept Radiol Phys, Boston, MA 02115 USA. RP Hunter, GJ (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St,Gray 273A, Boston, MA 02114 USA. EM gjhunter@partners.org NR 17 TC 12 Z9 12 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2014 VL 270 IS 1 BP 168 EP 175 DI 10.1148/radiol.13122851 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292QC UT WOS:000329916100021 PM 24009349 ER PT J AU Al-Hawary, MM Francis, IR Chari, ST Fishman, EK Hough, DM Lu, DS Macari, M Megibow, AJ Miller, FH Mortele, KJ Merchant, NB Minter, RM Tamm, EP Sahani, DV Simeone, DM AF Al-Hawary, Mahmoud M. Francis, Isaac R. Chari, Suresh T. Fishman, Elliot K. Hough, David M. Lu, David S. Macari, Michael Megibow, Alec J. Miller, Frank H. Mortele, Koenraad J. Merchant, Nipun B. Minter, Rebecca M. Tamm, Eric P. Sahani, Dushyant V. Simeone, Diane M. TI Pancreatic Ductal Adenocarcinoma Radiology Reporting Template: Consensus Statement of the Society of Abdominal Radiology and the American Pancreatic Association SO RADIOLOGY LA English DT Article ID DETERMINING RESECTABILITY; PREOPERATIVE THERAPY; MULTIDETECTOR CT; SECONDARY SIGNS; CANCER; MDCT; PANCREATICODUODENECTOMY; DIAGNOSIS; SURVIVAL; UPDATE AB Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions. (C) RSNA and the AGA Institute, 2014 C1 [Al-Hawary, Mahmoud M.; Francis, Isaac R.] Univ Michigan Hlth Syst, Univ Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. [Minter, Rebecca M.; Simeone, Diane M.] Univ Michigan Hlth Syst, Univ Hosp, Dept Surg, Ann Arbor, MI 48109 USA. [Simeone, Diane M.] Univ Michigan Hlth Syst, Univ Hosp, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Chari, Suresh T.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Hough, David M.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Fishman, Elliot K.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Lu, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Macari, Michael; Megibow, Alec J.] NYU, Med Ctr, Dept Radiol, New York, NY 10016 USA. [Miller, Frank H.] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Mortele, Koenraad J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. [Merchant, Nipun B.] Vanderbilt Univ, Dept Surg, Nashville, TN 37240 USA. [Tamm, Eric P.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Al-Hawary, MM (reprint author), Univ Michigan Hlth Syst, Univ Hosp, Dept Radiol, 1500 E Med Ctr Dr,Room B1 D502, Ann Arbor, MI 48109 USA. EM alhawary@med.umich.edu OI fishman, elliot/0000-0002-2567-1658 NR 40 TC 24 Z9 24 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2014 VL 270 IS 1 BP 248 EP 260 DI 10.1148/radiol.13131184 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292QC UT WOS:000329916100030 PM 24354378 ER PT J AU Karakis, I Montouris, GD Piperidou, C San Luciano, M Meador, KJ Cole, AJ AF Karakis, Ioannis Montouris, Georgia D. Piperidou, Charitomeni San Luciano, Marta Meador, Kimford J. Cole, Andrew J. TI Patient and caregiver quality of life in psychogenic non-epileptic seizures compared to epileptic seizures SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE Caregiver; Quality of life; Burden; Psychogenic non epileptic seizures; Epilepsy; Zarit burden interview; SF36v2 ID MONTREAL COGNITIVE ASSESSMENT; DAYTIME SLEEPINESS; GENDER-DIFFERENCES; DEPRESSION; ANXIETY; PEOPLE; ADULTS; DETERMINANTS; DISTURBANCE; POPULATION AB Purpose: Little is known about the effect of psychogenic non epileptic seizures (PNES) to caregiver quality of life (QOL), particularly as it compares to epileptic seizures (ES). We sought to characterize this effect and identify its determinants. Methods: The study population comprised of 126 ES and 33 PNES patients who underwent video EEG monitoring along with 48 and 18 caregivers respectively who accompanied them to their investigations. Patients completed questionnaires providing demographic, disease-related, cognitive, psychiatric, sleep and QOL information on admission, prior to their diagnosis being clarified. Their caregivers completed questionnaires providing demographic, disease burden and generic QOL information. Paraclinical data were also gathered. Regression analysis was used to identify patient and caregiver related determinants of patient and caregiver QOL. Results: QOL scores were significantly worse for PNES than ES patients and were mainly linked to depression levels. PNES and ES caregivers had comparable demographic characteristics and QOL scores. ES caregiver QOL was better in employed caregivers with lower burden scores for the physical component summary (PCS) and worse in female caregivers of depressed patients with higher burden scores for the mental component summary (MCS). Caregiver burden score was the strongest correlate of PNES caregiver MCS QOL score. Conclusion: Caregiver QOL in PNES does not differ from caregiver QOL in ES, while patient QOL is worse in PNES. Caregiver burden emerges as a consistent correlate of caregiver QOL both in ES and PNES. These findings advocate for consideration of caregiver burden and QOL in PNES in clinical practice and for future research paradigms. (C) 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Karakis, Ioannis; Meador, Kimford J.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30303 USA. [Montouris, Georgia D.] Boston Univ, Sch Med, Boston Med Ctr, Dept Neurol, Boston, MA 02118 USA. [Piperidou, Charitomeni] Democritus Univ Thrace, Dept Neurol, Alexandroupolis, Greece. [San Luciano, Marta] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Cole, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA. RP Karakis, I (reprint author), Emory Univ, Sch Med, Dept Neurol, Fac Off Bldg,Grady Campus,49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 USA. EM ioannis.karakis@emory.edu NR 70 TC 9 Z9 11 U1 2 U2 10 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 EI 1532-2688 J9 SEIZURE-EUR J EPILEP JI Seizure PD JAN PY 2014 VL 23 IS 1 BP 47 EP 54 DI 10.1016/j.seizure.2013.09.011 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 293GZ UT WOS:000329960700010 PM 24140136 ER PT J AU Yang, L Froberg, JE Lee, JT AF Yang, Lin Froberg, John E. Lee, Jeannie T. TI Long noncoding RNAs: fresh perspectives into the RNA world SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review DE Long noncoding RNA; next-generation sequencing; epigenetics; therapeutics ID X-CHROMOSOME; HUMAN GENOME; WIDESPREAD TRANSCRIPTION; WIDE IDENTIFICATION; RAPID EVOLUTION; GENE-EXPRESSION; BINDING-SITES; HUMAN-CELLS; XIST RNA; B2 RNA AB Large-scale mapping of transcriptomes has revealed significant levels of transcriptional activity within both unannotated and annotated regions of the genome. Interestingly, many of the novel transcripts demonstrate tissue-specific expression and some level of sequence conservation across species, but most have low protein-coding potential. Here, we describe progress in identifying and characterizing long noncoding RNAs (IncRNAs) and review how these transcripts interact with other biological molecules to regulate diverse cellular processes. We also preview emerging techniques that will help advance the discovery and characterization of novel transcripts. Finally, we discuss the role of IncRNAs in disease and therapeutics. C1 [Yang, Lin; Froberg, John E.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Yang, Lin; Froberg, John E.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yang, Lin; Froberg, John E.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Agency for Science, Technology, and Research, Singapore; National Science Foundation; National Institutes of Health [R01-GM58839, R01-GM090278] FX We thank members of the laboratory for helpful discussions, and we apologize to any of our colleagues whose work could not be cited owing to space constraints. L.Y. is supported by the Agency for Science, Technology, and Research, Singapore. J.F.F. is supported by a National Science Foundation Graduate Research Fellowship. J.T.L is supported by the National Institutes of Health (R01-GM58839, R01-GM090278). J.T.L. is an investigator of the Howard Hughes Medical Institute. NR 100 TC 89 Z9 98 U1 10 U2 60 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 2014 VL 39 IS 1 BP 35 EP 43 DI 10.1016/j.tibs.2013.10.002 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293VB UT WOS:000330000700005 PM 24290031 ER PT J AU Biederman, J Petty, C Spencer, TJ Woodworth, KY Bhide, P Zhu, JM Faraone, SV AF Biederman, Joseph Petty, Carter Spencer, Thomas J. Woodworth, K. Yvonne Bhide, Pradeep Zhu, Jinmin Faraone, Stephen V. TI Is ADHD a risk for posttraumatic stress disorder (PTSD)? Results from a large longitudinal study of referred children with and without ADHD SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE Nicotine; Smoking; Anxiety; PTSD; ADHD ID ATTENTION-DEFICIT HYPERACTIVITY; FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; COMORBIDITY; BRAIN AB Objectives. Preclinical studies link prenatal nicotine exposure with the development of both ADHD-like phenotype in rodents and blockade of extinction learning in a fear conditioning paradigm, a preclinical model of posttraumatic stress disorder (PTSD). While these findings suggest that either ADHD, prenatal nicotine exposure, or both could be a risk factor for PTSD, such associations have not been investigated in humans. Methods. Subjects were ascertained from family-genetic, longitudinal studies of paediatrically and psychiatrically referred children with and without ADHD of both sexes and their siblings followed for 10 years from childhood into adulthood (n = 403 probands; n = 464 siblings; mean age at follow-up of probands and siblings = 22.0 years). All subjects were comprehensively evaluated with structured diagnostic interviews that included questions regarding prenatal use of cigarettes. Results. A total of 12% (104/867) of the sample had been exposed to maternal smoking during pregnancy. There was no interaction effect between maternal smoking during pregnancy and ADHD (z = 0.01, P = 0.99). Maternal smoking during pregnancy and ADHD were independent, significant risk factors for PTSD at the 10-year follow-up (odds ratio = 3.58 [1.35,9.48], z = 2.57, P = 0.01 and odds ratio = 2.23 [1.06,4.69], z = 2.11, P = 0.04, respectively). Conclusions. These results suggest that both maternal smoking during pregnancy and ADHD are significant predictors of PTSD in humans. C1 [Biederman, Joseph; Petty, Carter; Spencer, Thomas J.; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Petty, Carter; Spencer, Thomas J.; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Bhide, Pradeep; Zhu, Jinmin] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Bhide, Pradeep/0000-0003-4236-9415; Faraone, Stephen/0000-0002-9217-3982 FU MGH Psychiatry Academy; Eli Lilly; Shire; AstraZeneca; Elminda; Janssen; McNeil; Abbott; Alza; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Fundacion Areces (Spain); Forest; Glaxo; Gliatech; Hastings Center; Janssen, McNeil; Medice Pharmaceuticals (Germany); Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Shire Laboratories Inc; Eli Lilly Company; McNeil Pharmaceutical; Novartis Pharmaceuticals; Department of Defense; Alcobra; National Institutes of Health (NIH); National Institute of Health [R01 HD36317, R01 MH50657]; Pediatric Psychopharmacology Research Council Fund FX Dr Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2012, Dr. Joseph Biederman received an honorarium from the MGH Psychiatry Academy and The Children's Hospital of Southwest Florida/Lee Memorial Health System for tuition-funded CME courses. In 2011, Dr Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received an honorarium for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. Dr Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, Dr Biederman received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A. C. in Monterrey Mexico. Dr Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In previous years, Dr Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Fundacion Areces (Spain), Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth.; Dr Thomas Spencer has received research support from the following sources: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, NIMH and the Department of Defense. Dr Spencer has been a speaker or on a speaker's bureau for the following pharmaceutical companies: Shire Laboratories, Inc, McNeil Pharmaceutical, and Novartis Pharmaceuticals. Dr Spencer has been an advisor or on an advisory board for the following pharmaceutical companies: Alcobra, Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Janssen, McNeil Pharmaceutical, and Novartis Pharmaceuticals. Dr Spencer receives research support from Royalties and Licensing fees on copyrighted ADHD scales through MGH Corporate Sponsored Research and Licensing. Dr Spencer has a US Patent Application pending (Provisional Number #61/233,686), through MGH corporate licensing, on a method to prevent stimulant abuse.; In the past year, Dr Faraone received consulting income and/or research support from Shire, Otsuka and Alcobra and research support from the National Institutes of Health (NIH). He is also on the Clinical Advisory Board for Akili Interactive Labs. In previous years, he received consulting fees or was on Advisory Boards or participated in continuing medical education programs sponsored by: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. Dr Faraone receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health and Oxford University Press: Schizophrenia: The Facts; This manuscript was supported in part by grants to J. Biederman from the National Institute of Health (R01 HD36317, R01 MH50657) and the Pediatric Psychopharmacology Research Council Fund. NR 19 TC 5 Z9 5 U1 2 U2 22 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1562-2975 EI 1814-1412 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PD JAN PY 2014 VL 15 IS 1 BP 49 EP 55 DI 10.3109/15622975.2012.756585 PG 7 WC Psychiatry SC Psychiatry GA 291KT UT WOS:000329828300006 PM 23607442 ER PT J AU Asch, DA Nicholson, S Srinivas, SK Herrin, J Epstein, AJ AF Asch, David A. Nicholson, Sean Srinivas, Sindhu K. Herrin, Jeph Epstein, Andrew J. TI How Do You Deliver a Good Obstetrician? Outcome-Based Evaluation of Medical Education SO ACADEMIC MEDICINE LA English DT Editorial Material AB The goal of medical education is the production of a workforce capable of improving the health and health care of patients and populations, but it is hard to use a goal that lofty, that broad, and that distant as a standard against which to judge the success of schools or training programs or particular elements within them. For that reason, the evaluation of medical education often focuses on elements of its structure and process, or on the assessment of competencies that could be considered intermediate outcomes. These measures are more practical because they are easier to collect, and they are valuable when they reflect activities in important positions along the pathway to clinical outcomes. But they are all substitutes for measuring whether educational efforts produce doctors who take good care of patients. The authors argue that the evaluation of medical education can become more closely tethered to the clinical outcomes medical education aims to achieve. They focus on a specific clinical outcomematernal complications of obstetrical deliveryand show how examining various observable elements of physicians' training and experience helps reveal which of those elements lead to better outcomes. Does it matter where obstetricians trained? Does it matter how much experience they have? Does it matter how good they were to start? Each of these questions reflects a component of the production of a good obstetrician and, most important, defines a good obstetrician as one whose patients in the end do well. C1 [Asch, David A.; Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Asch, David A.; Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Penn Med Ctr Hlth Care Innovat, Philadelphia, PA USA. [Nicholson, Sean] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA. [Nicholson, Sean] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Srinivas, Sindhu K.] Univ Penn, Div Maternal Fetal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Herrin, Jeph] Yale Univ, Sch Med, New Haven, CT USA. [Herrin, Jeph] Hlth Res Educ Trust, Chicago, IL USA. RP Asch, DA (reprint author), Ctr Innovat, 423 Guardian Dr Blockley Hall 1123, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X NR 3 TC 14 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JAN PY 2014 VL 89 IS 1 BP 24 EP 26 DI 10.1097/ACM.0000000000000067 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 282RI UT WOS:000329189900011 PM 24280859 ER PT J AU Shahian, DM Liu, X Meyer, GS Normand, SLT AF Shahian, David M. Liu, Xiu Meyer, Gregg S. Normand, Sharon-Lise T. TI Comparing Teaching Versus Nonteaching Hospitals: The Association of Patient Characteristics With Teaching Intensity for Three Common Medical Conditions SO ACADEMIC MEDICINE LA English DT Article ID QUALITY-OF-CARE; ACUTE MYOCARDIAL-INFARCTION; 30-DAY MORTALITY-RATES; INTERHOSPITAL TRANSFERS; ETHNIC DISPARITIES; CRITICALLY-ILL; RACIAL-DIFFERENCES; PROPENSITY SCORE; REFERRAL CENTER; HEART-FAILURE AB Purpose To quantify the role of teaching hospitals in direct patient care, the authors compared characteristics of patients served by hospitals of varying teaching intensity. Method The authors studied Medicare beneficiaries 66 years old, hospitalized in 2009-2010 for acute myocardial infarction, heart failure, or pneumonia. They categorized hospitals as nonteaching, teaching, or Council of Teaching Hospitals and Health Systems (COTH) members and performed secondary analyses using intern and resident-to-bed ratios. The authors used descriptive statistics, adjusted odds ratios, and linear propensity scores to compare patient characteristics among teaching intensity levels. They supplemented Medicare mortality model variables with race, transfer status, and distance traveled. Results Adjusted for comorbidities, black patients had 2.44 (95% confidence interval [CI] 2.36-2.52), 2.56 (95% CI 2.51-2.60), and 2.58 (95% CI 2.51-2.65) times the odds of COTH hospital admission compared with white patients for acute myocardial infarction, heart failure, and pneumonia, respectively. For patients transferred from another hospital's inpatient setting, the corresponding adjusted odds ratios of COTH hospital admission were 3.99 (95% CI 3.85-4.13), 4.60 (95% CI 4.34-4.88), and 4.62 (95% CI 4.16-5.12). Using national data, distributions of propensity scores (probability of admission to a COTH hospital) varied markedly among teaching intensity levels. Data from Massachusetts and California illustrated between-state heterogeneity in COTH utilization. Conclusions Major teaching hospitals are significantly more likely to provide care for minorities and patients requiring transfer from other institutions for advanced care.Both are essential to an equitable and high-quality regional health care system. C1 [Shahian, David M.; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Shahian, David M.; Liu, Xiu] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Meyer, Gregg S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 51 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JAN PY 2014 VL 89 IS 1 BP 94 EP 106 DI 10.1097/ACM.0000000000000050 PG 13 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 282RI UT WOS:000329189900027 PM 24280849 ER PT J AU Co, JPT AF Co, John Patrick T. TI Educating for Quality: Quality Improvement as an Activity of Daily Learning to Improve Educational and Patient Outcomes SO ACADEMIC PEDIATRICS LA English DT Editorial Material C1 [Co, John Patrick T.] Partners HlealthCare, Off Grad Med Educ, Boston, MA USA. [Co, John Patrick T.] MassGen Hosp Children, Dept Pediat Outpatient Qual & Safety, Boston, MA 02114 USA. RP Co, JPT (reprint author), MassGen Hosp Children, 7 Whittier Pl,Suite 108, Boston, MA 02114 USA. EM jco@partners.org NR 11 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2014 VL 14 IS 1 BP 1 EP 3 PG 3 WC Pediatrics SC Pediatrics GA 287SS UT WOS:000329563100001 PM 24369861 ER PT J AU Craig, MS Garfunkel, LC Baldwin, CD Mann, KJ Moses, JM Co, JPT Blumkin, AK Szilagyi, PG AF Craig, Mark S. Garfunkel, Lynn C. Baldwin, Constance D. Mann, Keith J. Moses, James M. Co, John Patrick T. Blumkin, Aaron K. Szilagyi, Peter G. TI Pediatric Resident Education in Quality Improvement (QI): A National Survey SO ACADEMIC PEDIATRICS LA English DT Article DE education; effectiveness; pediatrics; quality improvement; resident; self-efficacy ID PATIENT SAFETY; RESPONSE RATES; PHYSICIANS; VALIDATION; KNOWLEDGE AB OBJECTIVE: To assess pediatric residents' perceptions of their quality improvement (QI) education and training, including factors that facilitate learning QI and self-efficacy in QI activities. METHODS: A 22-question survey questionnaire was developed with expert-identified key topics and iterative pretesting of questions. Third-year pediatric residents from 45 residency programs recruited from a random sample of 120 programs. Data were analyzed by descriptive statistics, chi-square tests, and qualitative content analysis. RESULTS: Respondents included 331 residents for a response rate of 47%. Demographic characteristics resembled the national profile of pediatric residents. Over 70% of residents reported that their QI training was well organized and met their needs. Three quarters felt ready to use QI methods in practice. Those with QI training before residency were significantly more confident than those without prior QI training. However, fewer than half of respondents used standard QI methods such as PDSA cycles and run charts in projects. Residents identified faculty support, a structured curriculum, hands-on projects, and dedicated project time as key strengths of their QI educational experiences. A strong QI culture was also considered important, and was reported to be present in most programs sampled. CONCLUSIONS: Overall, third-year pediatric residents reported positive QI educational experiences with strong faculty support and sufficient time for QI projects. However, a third of residents thought that the QI curricula in their programs needed improvement, and a quarter lacked self-efficacy in conducting future QI activities. Continuing curricular improvement, including faculty development, is warranted. C1 [Craig, Mark S.; Baldwin, Constance D.; Blumkin, Aaron K.; Szilagyi, Peter G.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. [Craig, Mark S.] Madigan Army Med Ctr, Dept Pediat, Tacoma, WA 98431 USA. [Garfunkel, Lynn C.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. [Garfunkel, Lynn C.] Rochester Gen Hosp, Rochester, NY 14621 USA. [Mann, Keith J.] Childrens Mercy Hosp & Clin, Dept Pediat, Kansas City, MO USA. [Mann, Keith J.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Moses, James M.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Moses, James M.] Boston Med Ctr, Boston, MA USA. [Co, John Patrick T.] Partners HealthCare, Off Grad Med Educ, Boston, MA USA. [Co, John Patrick T.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Craig, MS (reprint author), 28 Madrona Pl, Dupont, WA 98327 USA. EM markscraig2004@yahoo.com OI Moses, James/0000-0002-5366-7816 FU Association of Pediatric Program Directors (APPD) FX Funded by an Association of Pediatric Program Directors (APPD) Special Project grant. NR 24 TC 5 Z9 5 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2014 VL 14 IS 1 BP 54 EP 61 PG 8 WC Pediatrics SC Pediatrics GA 287SS UT WOS:000329563100010 PM 24369869 ER PT J AU Dysken, MW Guarino, PD Vertrees, JE Asthana, S Sano, M Llorente, M Pallaki, M Love, S Schellenberg, GD McCarten, JR Malphurs, J Prieto, S Cheng, PJ Loreck, DJ Carneyk, S Trapp, G Bakshi, RS Mintzer, JE Heidebrink, JL Vidal-Cardona, A Arroyo, LM Cruz, AR Kowall, NW Chopra, MP Craft, S Thielke, S Turvey, CL Woodman, C Monnell, KA Gordon, K Tomaska, J Vatassery, G AF Dysken, Maurice W. Guarino, Peter D. Vertrees, Julia E. Asthana, Sanjay Sano, Mary Llorente, Maria Pallaki, Muralidhar Love, Susan Schellenberg, Gerard D. McCarten, J. Riley Malphurs, Julie Prieto, Susana Cheng, Peijun Loreck, David J. Carneyk, Sara Trapp, George Bakshi, Rajbir S. Mintzer, Jacobo E. Heidebrink, Judith L. Vidal-Cardona, Ana Arroyo, Lillian M. Cruz, Angel R. Kowall, Neil W. Chopra, Mohit P. Craft, Suzanne Thielke, Stephen Turvey, Carolyn L. Woodman, Catherine Monnell, Kimberly A. Gordon, Kimberly Tomaska, Julie Vatassery, Govind TI Vitamin E and memantine in Alzheimer's disease: Clinical trial methods and baseline data SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Alpha-tocopherol; Vitamin E; Memantine; Cholinesterase inhibitors; Randomized trials ID RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; COGNITIVE DECLINE; PROSTATE-CANCER; CO-MORBIDITY; MODERATE; PLACEBO; SUPPLEMENTATION; PREVENTION; INVENTORY AB Background: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. Methods: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. Results: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. Conclusion: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Dysken, Maurice W.; Love, Susan; McCarten, J. Riley; Tomaska, Julie; Vatassery, Govind] VA Minneapolis Hlth Care Syst, Minneapolis, MN 55417 USA. [Guarino, Peter D.] VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Vertrees, Julia E.] Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA. [Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, New York, NY USA. [Sano, Mary] Bronx Vet Med Res Ctr, New York, NY USA. [Llorente, Maria] VAMC, Washington, DC USA. [Pallaki, Muralidhar; Cheng, Peijun] Louis Stokes Cleveland VAMC, Cleveland, OH USA. [Schellenberg, Gerard D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Malphurs, Julie; Prieto, Susana] VA Miami Healthcare Syst, Miami, FL USA. [Loreck, David J.] Univ Maryland, Sch Med, Dept Psychiat, VA Maorland Healthcare Syst, Baltimore, MD 21201 USA. [Carneyk, Sara] VA Maryland Healthcare Syst, Baltimore, MD USA. [Trapp, George; Bakshi, Rajbir S.] VA NorthTexas Healthcare Syst, Dallas, TX USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. [Heidebrink, Judith L.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Vidal-Cardona, Ana; Arroyo, Lillian M.] VA Caribbean Healthcare Syst, San Juan, PR USA. [Cruz, Angel R.] Bay Pines VA Healthcare Syst, Bay Pines, FL USA. [Kowall, Neil W.; Chopra, Mohit P.] VA Boston Healthcare Syst, Boston, MA USA. [Craft, Suzanne; Thielke, Stephen] Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. [Turvey, Carolyn L.; Woodman, Catherine] Univ Iowa, Iowa City VAMC, Iowa City, IA USA. [Monnell, Kimberly A.; Gordon, Kimberly] WG Bill Hefner VAMC, Salisbury, NC USA. RP Dysken, MW (reprint author), VA Minneapolis Hlth Care Syst, Minneapolis, MN 55417 USA. EM maurice.dysken@va.gov RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU Department of Veterans Affairs Cooperative Studies Program [546]; Arista Industries, Inc.; Department of Veterans Affairs Cooperative Studies Program FX The VA Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)(CSP #546) was funded by the Department of Veterans Affairs Cooperative Studies Program. Forest Research Institute, a Division of Forest Laboratories, Inc., donated the memantine and matching placebo tablets. DSM Nutritional Products, Inc., donated the dl-alpha-tocopheryl acetate oil and funding for the purchase of the soybean oil from Arista Industries, Inc. The Department of Veterans Affairs Cooperative Studies Program, as sponsor of the trial, participated in the design and oversaw the conduct of the study but had no input into data collection, management, analysis, and interpretation of the data or preparation, review, or approval of the manuscript. NR 41 TC 8 Z9 8 U1 2 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2014 VL 10 IS 1 BP 36 EP 44 DI 10.1016/j.jalz.2013.01.014 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 287RG UT WOS:000329559300005 PM 23583234 ER PT J AU Fox, E AF Fox, Ellen TI Developing a Certifying Examination for Health Care Ethics Consultants: Bioethicists Need Help SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID NATIONAL-SURVEY; HOSPITALS C1 [Fox, Ellen] Natl Ctr Eth Hlth Care, US Dept Vet Affairs, Washington, DC 20420 USA. RP Fox, E (reprint author), Natl Ctr Eth Hlth Care, US Dept Vet Affairs VA, 810 Vermont Ave,NW 10P6, Washington, DC 20420 USA. EM foxe2@comcast.net NR 12 TC 4 Z9 4 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JAN 1 PY 2014 VL 14 IS 1 BP 1 EP 4 DI 10.1080/15265161.2014.873243 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 288IH UT WOS:000329604700002 PM 24422919 ER PT J AU Garcia-Aymerich, J Varraso, R Danaei, G Camargo, CA Hernan, MA AF Garcia-Aymerich, Judith Varraso, Raphaelle Danaei, Goodarz Camargo, Carlos A., Jr. Hernan, Miguel A. TI Incidence of Adult-onset Asthma After Hypothetical Interventions on Body Mass Index and Physical Activity: An Application of the Parametric G-Formula SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE asthma; body mass index; g-formula; hypothetical interventions; physical activity ID OBSTRUCTIVE PULMONARY-DISEASE; CORONARY-HEART-DISEASE; RISK-FACTORS; CAUSAL INFERENCE; WOMEN; OBESITY; COHORT; QUESTIONNAIRE; MIDLIFE; LIFE AB High body mass index (BMI) (calculated as weight (kg)/height (m)(2)) is associated with increased asthma risk, but uncertainty persists about the role of physical activity. We estimated the independent and joint associations of hypothetical interventions on BMI and physical activity with the risk of adult-onset asthma in 76,470 asthma-free women from the Nurses Health Study who were followed between 1988 and 1998. Information about asthma, BMI, physical activity, and other factors was updated every 2 years. We used the parametric g-formula to estimate the 10-year asthma risk in the following 4 scenarios: no intervention, 5 BMI reduction in a 2-year period for those who were overweight or obese, at least 2.5 hours/week of moderate-to-vigorous physical activity, and both of the previous 2 interventions. At baseline, women had a mean age of 55 (standard deviation, 7) years and a mean BMI of 25.4 (standard deviation, 4.8). Median time spent in physical activity was 0.7 hours/week. During follow-up, 1,146 women developed asthma. The 10-year asthma risk under no intervention was 1.5. Compared with no intervention, the population risk ratios were 0.96 (95 confidence interval (CI): 0.93, 0.99) under the BMI intervention, 0.96 (95 CI: 0.81, 1.10) under the physical activity intervention, and 0.92 (95 CI: 0.78, 1.06) under the joint intervention. Interventions on BMI and physical activity may have a modest impact on the risk of adult-onset asthma in this population of US women. C1 [Garcia-Aymerich, Judith] Ctr Res Environm Epidemiol, Barcelona 08003, Spain. [Garcia-Aymerich, Judith] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Garcia-Aymerich, Judith] CIBER Epidemiol & Salud Publ, Barcelona, Spain. [Varraso, Raphaelle] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Resp & Environm Epidemiol Team, Villejuif, France. [Varraso, Raphaelle] Univ Paris 11, UMRS 1018, Villejuif, France. [Danaei, Goodarz; Camargo, Carlos A., Jr.; Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Danaei, Goodarz] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hernan, Miguel A.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Garcia-Aymerich, J (reprint author), Ctr Res Environm Epidemiol, Barcelona Biomed Res Pk,Dr Aiguader 88, Barcelona 08003, Spain. EM jgarcia@creal.cat RI Garcia-Aymerich, J/G-6867-2014; Varraso, Raphaelle/R-8740-2016 OI Garcia-Aymerich, J/0000-0002-7097-4586; Varraso, Raphaelle/0000-0002-3338-7825 FU US National Institutes of Health [R01 HL080644, CA-87969, HL-63841, AI-52338]; Spanish Ministry of Science and Innovation [J0C2009-00182]; Catalan Society of Pneumology; Spanish Society of Pneumology [2010/847] FX This work was supported by the US National Institutes of Health (grants R01 HL080644, CA-87969, HL-63841, and AI-52338); and mobility grants from the "Jose Castillejo" Spanish Ministry of Science and Innovation (J0C2009-00182), Catalan Society of Pneumology, and Spanish Society of Pneumology (2010/847) to J.G.A. NR 30 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2014 VL 179 IS 1 BP 20 EP 26 DI 10.1093/aje/kwt229 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 280WI UT WOS:000329061100005 PM 24107616 ER PT J AU Gilley, SK Stenbit, AE Pasek, RC Sas, KM Steele, SL Amria, M Bunni, MA Estell, KP Schwiebert, LM Flume, P Gooz, M Haycraft, CJ Yoder, BK Miller, C Pavlik, JA Turner, GA Sisson, JH Bell, PD AF Gilley, Sandra K. Stenbit, Antine E. Pasek, Raymond C. Sas, Kelli M. Steele, Stacy L. Amria, May Bunni, Marlene A. Estell, Kimberly P. Schwiebert, Lisa M. Flume, Patrick Gooz, Monika Haycraft, Courtney J. Yoder, Bradley K. Miller, Caroline Pavlik, Jacqueline A. Turner, Grant A. Sisson, Joseph H. Bell, P. Darwin TI Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE bronchiectasis; hyperreactivity; lung; respiratory ID POLYCYSTIC KIDNEY-DISEASE; SMOOTH-MUSCLE-CELLS; CALCIUM; MODEL; LUNG; INTRAFLAGELLAR; TRANSPORT; SPECTRUM; BIOLOGY; PROTEIN AB The mechanisms for the development of bronchiectasis and airway hyperreactivity have not been fully elucidated. Although genetic, acquired diseases and environmental influences may play a role, it is also possible that motile cilia can influence this disease process. We hypothesized that deletion of a key intraflagellar transport molecule, IFT88, in mature mice causes loss of cilia, resulting in airway remodeling. Airway cilia were deleted by knockout of IFT88, and airway remodeling and pulmonary function were evaluated. In IFT88(-) mice there was a substantial loss of airway cilia on respiratory epithelium. Three months after the deletion of cilia, there was clear evidence for bronchial remodeling that was not associated with inflammation or apparent defects in mucus clearance. There was evidence for airway epithelial cell hypertrophy and hyperplasia. IFT88(-) mice exhibited increased airway reactivity to a methacholine challenge and decreased ciliary beat frequency in the few remaining cells that possessed cilia. With deletion of respiratory cilia there was a marked increase in the number of club cells as seen by scanning electron microscopy. We suggest that airway remodeling may be exacerbated by the presence of club cells, since these cells are involved in airway repair. Club cells may be prevented from differentiating into respiratory epithelial cells because of a lack of IFT88 protein that is necessary to form a single nonmotile cilium. This monocilium is a prerequisite for these progenitor cells to transition into respiratory epithelial cells. In conclusion, motile cilia may play an important role in controlling airway structure and function. C1 [Gilley, Sandra K.; Stenbit, Antine E.; Sas, Kelli M.; Steele, Stacy L.; Amria, May; Bunni, Marlene A.; Flume, Patrick; Gooz, Monika; Haycraft, Courtney J.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Bell, P. Darwin] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Miller, Caroline] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN USA. [Pasek, Raymond C.; Estell, Kimberly P.; Schwiebert, Lisa M.; Yoder, Bradley K.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. [Pavlik, Jacqueline A.; Turner, Grant A.; Sisson, Joseph H.] Univ Nebraska, Med Ctr, Dept Internal Med, Pulm Crit Care Sleep & Allergy Div, Omaha, NE USA. RP Bell, PD (reprint author), Med Univ S Carolina, 70 President St,DDB520, Charleston, SC 29425 USA. EM Bellpd@musc.edu OI Pasek, Raymond/0000-0002-1817-8697 FU Veterans Affairs Merit Grant; Core C of the UAB [P30-DK-074038, DK-32032, DK-065655, RO1-AA-008769]; Dialysis Clinic FX This project was supported by a Veterans Affairs Merit Grant (P. D. Bell), Core C of the UAB P30-DK-074038, DK-32032 (P. D. Bell), DK-065655 (B. K. Yoder), RO1-AA-008769 (J. H. Sisson), and funds from Dialysis Clinic. NR 38 TC 8 Z9 9 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2014 VL 306 IS 2 BP L162 EP L169 DI 10.1152/ajplung.00095.2013 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 291VC UT WOS:000329858000006 PM 24213915 ER PT J AU Vagefi, PA AF Vagefi, Parsia A. TI In Utero Creation of Chimeric Liver Xenografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 23-26, 2014 CL Miami, FL SP Amer Soc Transplant Surg C1 [Vagefi, Parsia A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 SU 2 BP 61 EP 62 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 279ZZ UT WOS:000328999400021 ER PT J AU Uygun, B Ozer, S Bruinsma, B Rodriguez, D Martins, P Uygun, K Yarmush, M AF Uygun, Basak Ozer, Sinan Bruinsma, Bote Rodriguez, Donald Martins, Paulo Uygun, Korkut Yarmush, Martin TI Tissue Engineered Human Liver Grafts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 23-26, 2014 CL Miami, FL SP Amer Soc Transplant Surg C1 [Uygun, Basak; Ozer, Sinan; Bruinsma, Bote; Rodriguez, Donald; Uygun, Korkut; Yarmush, Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martins, Paulo] Univ Massachusetts, UMass Mem Med Ctr, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 SU 2 BP 63 EP 63 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 279ZZ UT WOS:000328999400026 ER PT J AU Michel, S Madariaga, M La Muraglia, G Villani, V Sekijima, M Farkash, E Allan, J Sachs, D Yamada, K Madsen, J AF Michel, Sebastian Madariaga, Maria La Muraglia, Glenn, II Villani, Vincenzo Sekijima, Mitsuhiro Farkash, Evan Allan, James Sachs, David Yamada, Kazuhiko Madsen, Joren TI Kidney-Induced Cardiac Allograft Tolerance Across a Full MHC-Barrier in Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 23-26, 2014 CL Miami, FL SP Amer Soc Transplant Surg C1 [Michel, Sebastian; Madariaga, Maria; La Muraglia, Glenn, II; Villani, Vincenzo; Sekijima, Mitsuhiro; Farkash, Evan; Allan, James; Sachs, David; Yamada, Kazuhiko; Madsen, Joren] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 SU 2 BP 70 EP 70 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 279ZZ UT WOS:000328999400045 ER PT J AU Adler, J Pratt, J Werger, N Marquez, A Nguyen, L Markmann, J Yeh, H AF Adler, Joel Pratt, Joanne Werger, Nichole Marquez, Angela Nguyen, Louis Markmann, James Yeh, Heidi TI Socioeconomic Disparities among Deceased Donors and Kidney Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 23-26, 2014 CL Miami, FL SP Amer Soc Transplant Surg C1 [Adler, Joel; Pratt, Joanne; Werger, Nichole; Marquez, Angela; Markmann, James; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nguyen, Louis] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 SU 2 BP 71 EP 71 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 279ZZ UT WOS:000328999400046 ER PT J AU Patel, M Kandula, P Markmann, J Vagefi, P AF Patel, Madhukar Kandula, Praveen Markmann, James Vagefi, Parsia TI Preoperative Screening for Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 23-26, 2014 CL Miami, FL SP Amer Soc Transplant Surg C1 [Patel, Madhukar; Kandula, Praveen; Markmann, James; Vagefi, Parsia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 SU 2 BP 84 EP 84 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 279ZZ UT WOS:000328999400087 ER PT J AU Grijalva, J Huizenga, M Camargo, F Sadri-Vakili, G Vakili, K AF Grijalva, James Huizenga, Megan Camargo, Fernando Sadri-Vakili, Ghazaleh Vakili, Khashayar TI Alterations in Hippo Signaling Pathway During Liver Regeneration SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) CY JAN 23-26, 2014 CL Miami, FL SP Amer Soc Transplant Surg C1 [Huizenga, Megan; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grijalva, James; Camargo, Fernando; Vakili, Khashayar] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 SU 2 BP 91 EP 92 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 279ZZ UT WOS:000328999400107 ER PT J AU Rice, LA Smith, I Kelleher, AR Greenwald, K Boninger, ML AF Rice, Laura A. Smith, Ian Kelleher, Annmaire R. Greenwald, Karen Boninger, Michael L. TI Impact of a Wheelchair Education Protocol Based on Practice Guidelines for Preservation of Upper-Limb Function: A Randomized Trial SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Medical education; Wheelchair; Rehabilitation; Spinal cord injuries ID SPINAL-CORD-INJURY; CARPAL-TUNNEL-SYNDROME; CLINICAL-PRACTICE GUIDELINES; BEARING UPPER EXTREMITY; PAIN RATING-SCALES; SHOULDER PAIN; RISK-FACTORS; PUSHRIM BIOMECHANICS; PARAPLEGIC PATIENTS; AXLE POSITION AB Objectives: To determine if strict use of the Paralyzed Veterans of America's Clinical Practice Guidelines for Preservation of Upper Limb Function affects wheelchair setup, selection, propulsion biomechanics, pain, satisfaction with life, and participation of individuals with new spinal cord injuries (SCIs). Design: Single blinded, randomized controlled trial. Setting: Model SCI systems rehabilitation facility and community. Participants: Volunteer sample of manual wheelchair users with new SCIs (N=37). Intervention: The intervention group was strictly educated on the clinical practice guideline by a physical therapist and an occupational therapist in an inpatient rehabilitation facility. The standard of care group received standard therapy services. Main Outcome Measures: Comparison of wheelchair setup, selection, propulsion biomechanics, pain, and Satisfaction With Life Scale and Craig Handicap Assessment and Reporting Technique scores at the time of discharge from inpatient rehabilitation and at 6 months and 1 year postdischarge. Results: Participants in the intervention group pushed on tile with significantly lower push frequency (P=.02) at the discharge visit. On the ramp, the intervention group used a significantly larger push length (P =.03) across all time points. No significant differences were found between groups related to wheelchair setup, selection, pain, satisfaction with life, and participation. Conclusions: The intervention group showed better skills on key wheelchair propulsion biomechanics variables related to upper-limb health. Use of a structured education program may be an effective method of educating new manual wheelchair users to prevent the development of upper-limb impairments in an inpatient setting. Additional follow-up testing is necessary to determine whether the differences seen in propulsion skills translate into decreased pain and improved quality of life in the long term. Archives of Physical Medicine and Rehabilitation 2014;95:10-9 (c) 2014 by the American Congress of Rehabilitation Medicine C1 [Boninger, Michael L.] Univ Illinois, Dept Kinesiol & Community Hlth, Urbana, IL 61801 USA. [Smith, Ian; Greenwald, Karen; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Kelleher, Annmaire R.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Kelleher, Annmaire R.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. RP Rice, LA (reprint author), 2003 Huff Hall,M-C-586,1206 South 4th St, Champaign, IL 61820 USA. EM ricela@illinois.edu OI Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability and Rehabilitation Research; Office of Special Education and Rehabilitation Services; US Department of Education [H133N000019, H133N060019] FX Supported by the National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, US Department of Education (grant no. H133N000019/ H133N060019). The material presented hem is solely the responsibility of the authors and does not necessarily reflect the opinions of the funding agency or the US Department of Education. NR 52 TC 0 Z9 0 U1 4 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2014 VL 95 IS 1 BP 10 EP 19 DI 10.1016/j.apmr.2013.06.028 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 289KI UT WOS:000329681000002 PM 23856151 ER PT J AU Gupta, V Malone, AK Hari, PN Ahn, KW Hu, ZH Gale, RP Ballen, KK Hamadani, M Olavarria, E Gerds, AT Waller, EK Costa, LJ Antin, JH Kamble, RT van Besien, KM Savani, BN Schouten, HC Szer, J Cahn, JY de Lima, MJ Wirk, B Aljurf, MD Popat, U Bejanyan, N Litzow, MR Norkin, M Lewis, ID Hale, GA Woolfrey, AE Miller, AM Ustun, C Jagasia, MH Lill, M Maziarz, RT Cortes, J Kalaycio, ME Saber, W AF Gupta, Vikas Malone, Adriana K. Hari, Parameswaran N. Ahn, Kwang Woo Hu, Zhen-Huan Gale, Robert Peter Ballen, Karen K. Hamadani, Mehdi Olavarria, Eduardo Gerds, Aaron T. Waller, Edmund K. Costa, Luciano J. Antin, Joseph H. Kamble, Rammurti T. van Besien, Koen M. Savani, Bipin N. Schouten, Harry C. Szer, Jeffrey Cahn, Jean-Yves de Lima, Marcos J. Wirk, Baldeep Aljurf, Mahmoud D. Popat, Uday Bejanyan, Nelli Litzow, Mark R. Norkin, Maxim Lewis, Ian D. Hale, Gregory A. Woolfrey, Ann E. Miller, Alan M. Ustun, Celalettin Jagasia, Madan H. Lill, Michael Maziarz, Richard T. Cortes, Jorge Kalaycio, Matt E. Saber, Wael TI Reduced-Intensity Hematopoietic Cell Transplantation for Patients with Primary Myelofibrosis: A Cohort Analysis from the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Myelofibrosis; Allogeneic transplantation; Reduced intensity; Prognosis ID PROGNOSTIC SCORING SYSTEM; MYELOID METAPLASIA; PREDICT SURVIVAL; WORKING GROUP; CHRONIC GRAFT; HOST-DISEASE; THERAPY; MODEL; RISK AB We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HO's, an HLA well-matched unrelated donor CURD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P =.002). The relative risk (RR) for NRM was 3.92 (P =.006) for well-matched URD and 9.37 (P <.0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P =.07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Gupta, Vikas] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Malone, Adriana K.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Hari, Parameswaran N.; Ahn, Kwang Woo; Hu, Zhen-Huan; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Sect Hematol, Div Expt Med, London, England. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hamadani, Mehdi] West Virginia Univ Hosp, Morgantown, WV USA. [Olavarria, Eduardo] Complejo Hosp Navarra, Dept Hematol, Pamplona, Spain. [Olavarria, Eduardo] Complejo Hosp Navarra, BMT Unit, Pamplona, Spain. [Gerds, Aaron T.; Woolfrey, Ann E.; Kalaycio, Matt E.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Waller, Edmund K.] Emory Univ Hosp, Bone Marrow & Stem Cell Transplant Ctr, Atlanta, GA 30322 USA. [Costa, Luciano J.] Med Univ S Carolina, Blood & Marrow Transplant Program, Charleston, SC 29425 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [van Besien, Koen M.] Weill Cornell Med Coll, Stem Cell Transplant Program, New York, NY USA. [Savani, Bipin N.; Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Schouten, Harry C.] Acad Ziekenhuis Maastricht, Maastricht, Netherlands. [Szer, Jeffrey] Royal Melbourne Hosp, Clin Haematol & BMT Serv, Melbourne, Vic, Australia. [Cahn, Jean-Yves] Univ Hosp, Dept Hematol, Grenoble, France. [de Lima, Marcos J.] Univ Hosp Cleveland, Case Med Ctr, Seidman Canc Ctr, Cleveland, OH 44106 USA. [Wirk, Baldeep; Norkin, Maxim] Shands HealthCare, Dept Hematol Oncol, Gainesville, FL USA. [Wirk, Baldeep; Norkin, Maxim] Univ Florida, Gainesville, FL USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Popat, Uday; Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bejanyan, Nelli; Ustun, Celalettin] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Litzow, Mark R.] Mayo Clin Rochester, Rochester, MN USA. [Lewis, Ian D.] Royal Adelaide Hosp SA Pathol, Haematol & Bone Marrow Transplant Unit, Adelaide, SA, Australia. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Miller, Alan M.] Baylor Univ, Med Ctr, Dallas, TX USA. [Lill, Michael] Cedars Sinai Med Ctr, Dept Hematol Oncol, Los Angeles, CA 90048 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. RP Gupta, V (reprint author), Princess Margaret Canc Ctr, 610 Univ Ave,Ste 5-217, Toronto, ON M5G2M9, Canada. EM vikas.gupta@uhn.on.ca RI Cahn, Jean-Yves/M-6493-2014; OI Hari, Parameswaran/0000-0002-8800-297X FU Public Health Service Grant from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) [U24 CA076518]; National Institute of Allergy and Infectious Diseases (NIAID); NHLBI and NCI [U10 HL069294]; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Allos Therapeutics; Amgen FX Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24 CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement U10 HL069294 from the NHLBI and NCI; Contract HHSH250201200016C with Health Resources and Services Administration; Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Allos Therapeutics, Amgen, anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association, Celgene, Fresenius-Biotech North America, Gamida Cell Teva Joint Venture, Genentech, Gentium, Genzyme, GlaxoSmithKline, HistoGenetics, Kiadis Pharma; Leukemia and Lymphoma Society, Medical College of Wisconsin; Merck & Co, Millennium: Takeda Oncology, Milliman USA, Miltenyi Biotec, National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Osiris Therapeutics, Otsuka America Pharmaceutical, Remedy Informatics, Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, StemCyte, Stemsoft Software, Swedish Orphan Biovitrum, Tarix Pharmaceuticals, TerumoBCT, Teva Neuroscience, Therakos, and Wellpoint. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, Department of the Navy, Department of Defense, or any other agency of the US Government. NR 24 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2014 VL 20 IS 1 BP 89 EP 97 DI 10.1016/j.bbmt.2013.10.018 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 289LG UT WOS:000329683400014 PM 24161923 ER PT J AU Switzer, GE Bruce, JG Harrington, D Haagenson, M Drexler, R Foley, A Confer, D Bishop, M Anderlini, P Rowley, S Leitman, SF Anasetti, C Wingard, JR AF Switzer, Galen E. Bruce, Jessica G. Harrington, Donna Haagenson, Michael Drexler, Rebecca Foley, Amy Confer, Dennis Bishop, Michelle Anderlini, Paolo Rowley, Scott Leitman, Susan F. Anasetti, Claudio Wingard, John R. TI Health-related Quality of Life of Bone Marrow versus Peripheral Blood Stem Cell Donors: A Prespecified Subgroup Analysis from a Phase III RCT-BMTCTN Protocol 0201 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Marrow versus peripheral blood stem cell donation; Unrelated hematopoietic stem cell donation; Randomized trial ID UNRELATED DONORS; PROSPECTIVE TRIAL; MOOD STATES; DONATION; EXPERIENCE; PROGRAM; TRANSPLANTATION; SAFETY; PRODUCT; PROFILE AB Hematopoietic stem cells can be procured from unrelated donors via either the bone marrow (BM) aspiration or peripheral blood stem cell (PBSC) collection methods. There is no evidence from prospective randomized trials in the unrelated donor setting about the relative health-related quality-of-life (HRQoL) benefits/costs to donors. The goals of this prospective longitudinal investigation were to describe and compare the donation-related HRQoL experiences of 332 BM and PBSC donors. Donors were interviewed before donation, 48 hours after donation, weekly until fully recovered, and at 6 and 12 months after donation. Before donation, BM donors had lower confusion, fewer concerns, and were more prepared for donation. Shortly after donation, BM donors reported more physical side effects. BM donors also reported more donation-related impact on their social activities. However, BM donors reported somewhat better psychological status and were more likely to indicate that the donation made their lives more meaningful. There were virtually no longer term differences in the experiences of the 2 donor groups, including no recovery time difference beginning 3 weeks after donation. Although BM donors may experience the process as more physically stressful and more psychologically beneficial in the short term, the longer term HRQoL consequences of BM and PBSC donors are similar. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation. C1 [Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Switzer, Galen E.; Bruce, Jessica G.; Harrington, Donna] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA 15213 USA. [Haagenson, Michael; Drexler, Rebecca; Foley, Amy; Confer, Dennis] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Haagenson, Michael] Natl Marrow Donor Program, Minneapolis, MN USA. [Bishop, Michelle; Wingard, John R.] Univ Florida, Coll Med, Gainesville, FL USA. [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rowley, Scott] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Leitman, Susan F.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Anasetti, Claudio] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Switzer, GE (reprint author), Univ Pittsburgh, 3501 Forbes Ave,Oxford Bld Suite 410, Pittsburgh, PA 15213 USA. EM SwitzerGE@upmc.edu FU National Heart, Lung, and Blood Institute; National Cancer Institute [U10HL069294]; Office of Naval Research; National Marrow Donor program FX Financial disclosure: Supported by a grant from the National Heart, Lung, and Blood Institute and the National Cancer Institute (U10HL069294), by the Office of Naval Research, and by the National Marrow Donor program. NR 24 TC 9 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2014 VL 20 IS 1 BP 118 EP 127 DI 10.1016/j.bbmt.2013.10.024 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 289LG UT WOS:000329683400018 PM 24184336 ER PT J AU Mathews, CA Scharf, JM Miller, LL Macdonald-Wallis, C Lawlor, DA Ben-Shlomo, Y AF Mathews, Carol A. Scharf, Jeremiah M. Miller, Laura L. Macdonald-Wallis, Corrie Lawlor, Debbie A. Ben-Shlomo, Yoav TI Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID LOW-BIRTH-WEIGHT; BODY-MASS INDEX; HYPERTENSIVE DISORDERS; SEGREGATION ANALYSIS; CHILDREN ALSPAC; RISK-FACTORS; PREGNANCY; PARENTS; SMOKING; EXPRESSION AB Background burette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. Aims. To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Method Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression. Results Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder. Conclusions This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors. C1 [Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, Program Genet & Epidemiol Neuropsychiat Symptoms, San Francisco, CA 94143 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Miller, Laura L.; Macdonald-Wallis, Corrie; Lawlor, Debbie A.; Ben-Shlomo, Yoav] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Macdonald-Wallis, Corrie; Lawlor, Debbie A.] Univ Bristol, Ctr Causal Anal Translat Epidemiol, MRC, Bristol BS8 1TH, Avon, England. RP Mathews, CA (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. EM cmathews@ippi.ucsf.edu OI Lawlor, Debbie A/0000-0002-6793-2262 FU UK medical Research Council; Wellcome Trust [092731]; University of Bristol FX The UK medical Research Council and the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and they will serve as guarantors for the contents of this paper. We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. NR 34 TC 20 Z9 21 U1 0 U2 7 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JAN PY 2014 VL 204 IS 1 BP 40 EP 45 DI 10.1192/bjp.bp.112.125468 PG 6 WC Psychiatry SC Psychiatry GA 289MH UT WOS:000329686100011 PM 24262815 ER PT J AU Li, WQ Han, JL Widlund, HR Correll, M Wang, YYE Quackenbush, J Mihm, MC Canales, AL Wu, SW Golub, T Hoshida, Y Hunter, DJ Murphy, G Kupper, TS Qureshi, AA AF Li, Wen-Qing Han, Jiali Widlund, Hans R. Correll, Mick Wang, Yaoyu E. Quackenbush, John Mihm, Martin C. Canales, Alvaro Laga Wu, Shaowei Golub, Todd Hoshida, Yujin Hunter, David J. Murphy, George Kupper, Thomas S. Qureshi, Abrar A. TI CXCR4 pathway associated with family history of melanoma SO CANCER CAUSES & CONTROL LA English DT Article DE Melanoma; Genetic pathway analysis; Genome-wide expression profiling ID CUTANEOUS MALIGNANT-MELANOMA; GENE-EXPRESSION; CDKN2A MUTATIONS; GROWTH-FACTOR; SKIN-CANCER; BRAF; PIGMENTATION; RISK; VARIANTS; SURVIVAL AB Genetic predisposition plays a major role in the etiology of melanoma, but known genetic markers only account for a limited fraction of family-history-associated melanoma cases. Expression microarrays have offered the opportunity to identify further genomic profiles correlated with family history of melanoma. We aimed to distinguish mRNA expression signatures between melanoma cases with and without a family history of melanoma. Based on the Nurses' Health Study, family history was defined as having one or more first-degree family members diagnosed with melanoma. Melanoma diagnosis was confirmed by reviewing pathology reports, and tumor blocks were collected by mail from across the USA. Genomic interrogation was accomplished through evaluating expression profiling of formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, on either a 6K or whole-genome (24K) Illumina gene chip. Gene set enrichment analysis was performed for each batch to determine the differentially enriched pathways and key contributing genes. The CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, including MAPK1, PLCG1, CRK, and PTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway and NRAS, BRAF mutation, or Breslow thickness of the primary melanoma cases. We found that the CXCR4 pathway might constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives. C1 [Li, Wen-Qing; Han, Jiali; Widlund, Hans R.; Wu, Shaowei; Kupper, Thomas S.; Qureshi, Abrar A.] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Han, Jiali; Hunter, David J.; Qureshi, Abrar A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Han, Jiali; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Correll, Mick; Wang, Yaoyu E.; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Canales, Alvaro Laga; Murphy, George] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Golub, Todd; Hoshida, Yujin] Harvard Univ, Sch Med, Broad Inst, Boston, MA 02115 USA. RP Qureshi, AA (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, 45 Francis St,221L, Boston, MA 02115 USA. EM aqureshi@bics.bwh.harvard.edu RI Li, Wenqing/N-2293-2014; Wu, Shaowei/G-6647-2015 OI Li, Wenqing/0000-0002-1283-4091; Wu, Shaowei/0000-0003-2680-6064 FU Department of Dermatology, Brigham; Women's Hospital, Boston, Massachusetts [P01 CA87969] FX We are grateful to Drs. Alisa M. Goldstein and Nan Hu at Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, for their comments on our revisions. We thank the participants and staff of the Nurses' Health Study, for their valuable contributions as well as the following state cancer registries for their help: A. L., A.Z., A. R., C. A., C.O., C. T., D. E., F. L., G. A., I. D., I. L., I.N., I. A., K.Y., L. A., M. E., M. D., M. A., M. I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P. A., R. I., S. C., T.N., T. X., V. A., W. A., W.Y. This work was supported by Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, a Nurses' Health Study Grant (P01 CA87969). The funding sources did not involve in the data collection, data analysis, manuscript writing, and review. NR 39 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2014 VL 25 IS 1 BP 125 EP 132 DI 10.1007/s10552-013-0315-9 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 284WG UT WOS:000329351700012 PM 24158781 ER PT J AU Vaickus, LJ Tambouret, R AF Vaickus, Louis J. Tambouret, Rosemary TI A Simplified Method for Assessing Cytotechnologist Workload SO CANCER CYTOPATHOLOGY LA English DT Article DE workload; efficiency; computer; cytotechnologist; automation ID RANDOMIZED CONTROLLED-TRIAL; GYNECOLOGIC CYTOLOGY AB BACKGROUNDExamining cytotechnologist workflow and how it relates to job performance and patient safety is important in determining guidelines governing allowable workloads. This report discusses the development of a software tool that significantly simplifies the process of analyzing cytotechnologist workload while simultaneously increasing the quantity and resolution of the data collected. METHODSThe program runs in Microsoft Excel and minimizes manual data entry and data transcription by automating as many tasks as is feasible. RESULTSData show the cytotechnologists tested were remarkably consistent in the amount of time it took them to screen a cervical cytology (Gyn) or a nongynecologic cytology (Non-Gyn) case and that this amount of time was directly proportional to the number of slides per case. Namely, the time spent per slide did not differ significantly in Gyn versus Non-Gyn cases (2163.4 seconds and 23524.6 seconds, respectively; P=.16). There was no significant difference in the amount of time needed to complete a Gyn case between the morning and the evening (314 +/- 4.7 seconds and 312 +/- 7.1 seconds; P=.39), but a significantly increased time spent screening Non-Gyn cases (slide-adjusted) in the afternoon hours (323 +/- 20.1 seconds and 454 +/- 67.6 seconds; P=.027), which was largely the result of significantly increased time spent on prescreening activities such as checking the electronic medical record (62 +/- 6.9 seconds and 145 +/- 36 seconds; P=.006). CONCLUSIONSThis Excel-based data collection tool generates highly detailed data in an unobtrusive manner and is highly customizable to the individual working environment and clinical climate. Cancer (Cancer Cytopathol) 2014;122:15-22. (c) 2013 American Cancer Society. A program was developed for collecting detailed information concerning cytopathologist workload. Data can be easily collected in a nonobtrusive manner in a real workplace at a high temporal resolution. C1 [Vaickus, Louis J.; Tambouret, Rosemary] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Vaickus, LJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 2, Boston, MA 02114 USA. EM lvaickus@partners.org NR 6 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JAN PY 2014 VL 122 IS 1 BP 15 EP 22 DI 10.1002/cncy.21364 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 287OD UT WOS:000329551200005 PM 24424751 ER PT J AU Pitman, MB Centeno, BA Daglilar, ES Brugge, WR Mino-Kenudson, M AF Pitman, Martha B. Centeno, Barbara A. Daglilar, Ebubekir S. Brugge, William R. Mino-Kenudson, Mari TI Cytological Criteria of High-Grade Epithelial Atypia in the Cyst Fluid of Pancreatic Intraductal Papillary Mucinous Neoplasms SO CANCER CYTOPATHOLOGY LA English DT Article DE pancreas; cytology; endoscopic ultrasound; fine-needle aspiration; intraductal papillary mucinous neoplasm; criteria; high-grade atypia ID FINE-NEEDLE-ASPIRATION; INTERNATIONAL CONSENSUS GUIDELINES; LESS-THAN-OR-EQUAL-TO-3 CM; DIFFERENTIAL-DIAGNOSIS; ADDS VALUE; MALIGNANCY; MANAGEMENT; TUMORS; PREDICTORS; CARCINOMA AB BACKGROUNDThe recognition of epithelial cells with high-grade atypia (HGA) in the cyst fluid of an intraductal papillary mucinous neoplasm (IPMN) identifies a cyst at high risk of invasive carcinoma. To the best of the authors' knowledge, the cytological features of HGA have not been systematically analyzed to define diagnostic criteria. METHODSCell groups from patients with histologically confirmed branch-duct IPMNs were evaluated by 2 cytopathologists with expertise in pancreatic cytology. A consensus interpretation categorized the cell groups as having either low-grade (LG) or high-grade (HG) morphology. Characteristics regarding cell size and architecture, nuclear and cytoplasmic features, and background necrosis were analyzed. Performance characteristics were assessed using the Fisher exact test at 95% confidence intervals. RESULTSSixty cell groups yielded 27 LG and 25 HG morphological groups. No consensus was reached for 8 groups, which were excluded from statistical analysis. Five features that were found to be significantly different between the LG and HG groups included: 1) cell size < a 12-m duodenal enterocyte for HG and size equal for LG; 2) an increased nuclear-to-cytoplasmic (N/C) ratio; 3) marked nuclear membrane abnormalities; 4) abnormal chromatin pattern; and 5) background necrosis. The 3 most accurate features for the identification of HGA were background necrosis (88%), abnormal chromatin pattern (84%), and an increased N/C ratio (82%). CONCLUSIONSIPMN cyst fluid at high-risk of malignancy can be recognized most accurately by the presence of epithelial cells with HGA showing an increased N/C ratio, an abnormal chromatin pattern, and background necrosis. Cancer (Cancer Cytopathol) 2014;122:40-47. (c) 2013 American Cancer Society. The recognition of epithelial cells with high-grade atypia in the cyst fluid of an intraductal papillary mucinous neoplasm identifies a cyst at high risk for invasive carcinoma. In the current study, the cytological criteria distinguishing low-grade from high-grade atypia are described after the systematic evaluation of cells from histologically confirmed intraductal papillary mucinous neoplasms. C1 [Pitman, Martha B.; Mino-Kenudson, Mari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Centeno, Barbara A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33612 USA. [Daglilar, Ebubekir S.; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Gastroenterol Div, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 45 TC 25 Z9 26 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JAN PY 2014 VL 122 IS 1 BP 40 EP 47 DI 10.1002/cncy.21344 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 287OD UT WOS:000329551200008 PM 23939829 ER PT J AU Faber, AC Coffee, EM Costa, C Dastur, A Ebi, H Hata, AN Yeo, AT Edelman, EJ Song, Y Tam, AT Boisvert, JL Milano, RJ Roper, J Kodack, DP Jain, RK Corcoran, RB Rivera, MN Ramaswamy, S Hung, KE Benes, CH Engelman, JA AF Faber, Anthony C. Coffee, Erin M. Costa, Carlotta Dastur, Anahita Ebi, Hiromichi Hata, Aaron N. Yeo, Alan T. Edelman, Elena J. Song, Youngchul Tam, Ah Ting Boisvert, Jessica L. Milano, Randy J. Roper, Jatin Kodack, David P. Jain, Rakesh K. Corcoran, Ryan B. Rivera, Miguel N. Ramaswamy, Sridhar Hung, Kenneth E. Benes, Cyril H. Engelman, Jeffrey A. TI mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1 SO CANCER DISCOVERY LA English DT Article ID BCL-2 FAMILY INHIBITOR; CELL LUNG-CANCER; SYNTHETIC LETHAL INTERACTIONS; CHRONIC LYMPHOCYTIC-LEUKEMIA; COLON-CANCER; PHASE-I; TRANSLATIONAL CONTROL; OBATOCLAX GX15-070; DRUG-SENSITIVITY; TARGETED THERAPY AB Colorectal cancers harboring KRAS or BRAF mutations are refractory to current targeted therapies. Using data from a high-throughput drug screen, we have developed a novel therapeutic strategy that targets the apoptotic machinery using the BCL-2 family inhibitor ABT-263 (navitoclax) in combination with a TORC1/2 inhibitor, AZD8055. This combination leads to efficient apoptosis specifically in KRAS- and BRAF-mutant but not wild-type (WT) colorectal cancer cells. This specific susceptibility results from TORC1/2 inhibition leading to suppression of MCL-1 expression in mutant, but not WT, colorectal cancers, leading to abrogation of BIM/MCL-1 complexes. This combination strategy leads to tumor regressions in both KRAS-mutant colorectal cancer xenograft and genetically engineered mouse models of colorectal cancer, but not in the corresponding KRAS-WT colorectal cancer models. These data suggest that the combination of BCL-2/BCL-XL inhibitors with TORC1/2 inhibitors constitutes a promising targeted therapy strategy to treat these recalcitrant cancers. SIGNIFICANCE: Effective targeted therapies directed against colorectal cancer with activating mutations in KRAS remain elusive. We have leveraged drug-screen data from a large panel of human colorectal cancers to uncover an effective, rational targeted therapy strategy that has preferential activity in colorectal cancers with KRAS or BRAF mutations. This combination may be developed for clinical testing. (C) 2013 AACR. C1 [Faber, Anthony C.; Costa, Carlotta; Dastur, Anahita; Ebi, Hiromichi; Hata, Aaron N.; Yeo, Alan T.; Edelman, Elena J.; Song, Youngchul; Tam, Ah Ting; Boisvert, Jessica L.; Milano, Randy J.; Corcoran, Ryan B.; Rivera, Miguel N.; Ramaswamy, Sridhar; Benes, Cyril H.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Faber, Anthony C.; Costa, Carlotta; Dastur, Anahita; Ebi, Hiromichi; Hata, Aaron N.; Yeo, Alan T.; Edelman, Elena J.; Song, Youngchul; Tam, Ah Ting; Boisvert, Jessica L.; Milano, Randy J.; Corcoran, Ryan B.; Rivera, Miguel N.; Ramaswamy, Sridhar; Benes, Cyril H.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Coffee, Erin M.; Roper, Jatin; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Dept Med, Boston, MA USA. [Rivera, Miguel N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Kodack, David P.; Jain, Rakesh K.] Massachusetts Gen Hosp, Steele Lab Tumor Biol, Charlestown, MA USA. [Kodack, David P.; Jain, Rakesh K.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, CNY 149,13th St,Room 7316, Boston, MA 02129 USA. EM jengelman@partners.org OI Ebi, Hiromichi/0000-0003-3155-7576 FU DF/HCC Gastrointestinal Cancer SPORE [P50 CA127003]; NIH [R01CA140594, R01CA137008, 1U54HG006097-01]; Wellcome Trust [086357]; Burroughs Wellcome Fund; Howard Hughes Medical Institute; American Cancer Society Postdoctoral Fellowship FX This was work was supported by DF/HCC Gastrointestinal Cancer SPORE P50 CA127003 (to J.A. Engelman), grants from the NIH: R01CA140594 (to J.A. Engelman), R01CA137008 (to J.A. Engelman), 1U54HG006097-01 (to C. H. Benes), a grant from the Wellcome Trust (086357; to C. H. Benes), awards from the Burroughs Wellcome Fund and the Howard Hughes Medical Institute (to M.N. Rivera), and an American Cancer Society Postdoctoral Fellowship (to A. C. Faber). NR 50 TC 44 Z9 46 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2014 VL 4 IS 1 BP 42 EP 52 DI 10.1158/2159-8290.CD-13-0315 PG 11 WC Oncology SC Oncology GA 285ZP UT WOS:000329434300022 PM 24163374 ER PT J AU Wagle, N Van Allen, EM Treacy, DJ Frederick, DT Cooper, ZA Taylor-Weiner, A Rosenberg, M Goetz, EM Sullivan, RJ Farlow, DN Friedrich, DC Anderka, K Perrin, D Johannessen, CM McKenna, A Cibulskis, K Kryukov, G Hodis, E Lawrence, DP Fisher, S Getz, G Gabriel, SB Carter, SL Flaherty, KT Wargo, JA Garraway, LA AF Wagle, Nikhil Van Allen, Eliezer M. Treacy, Daniel J. Frederick, Dennie T. Cooper, Zachary A. Taylor-Weiner, Amaro Rosenberg, Mara Goetz, Eva M. Sullivan, Ryan J. Farlow, Deborah N. Friedrich, Dennis C. Anderka, Kristin Perrin, Danielle Johannessen, Cory M. McKenna, Aaron Cibulskis, Kristian Kryukov, Gregory Hodis, Eran Lawrence, Donald P. Fisher, Sheila Getz, Gad Gabriel, Stacey B. Carter, Scott L. Flaherty, Keith T. Wargo, Jennifer A. Garraway, Levi A. TI MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition SO CANCER DISCOVERY LA English DT Article ID RAF INHIBITION; METASTATIC MELANOMA; IMPROVED SURVIVAL; V600E MUTATION; MEK INHIBITION; VEMURAFENIB; AMPLIFICATION; PROTEIN; CANCER AB Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP-ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. We performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on pretreatment and drug-resistant tumors from five patients with acquired resistance to dabrafenib/trametinib. In three of these patients, we identified additional mitogen-activated protein kinase (MAPK) pathway alterations in the resistant tumor that were not detected in the pretreatment tumor, including a novel activating mutation in MEK2 (MEK2 Q60P). MEK2 Q60P conferred resistance to combined RAF/MEK inhibition in vitro, but remained sensitive to inhibition of the downstream kinase extracellular signal-regulated kinase (ERK). The continued MAPK signaling-based resistance identified in these patients suggests that alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma. SIGNIFICANCE: This study represents an initial clinical genomic study of acquired resistance to combined RAF/MEK inhibition in BRAF-mutant melanoma, using WES and RNA-seq. The presence of diverse resistance mechanisms suggests that serial biopsies and genomic/molecular profiling at the time of resistance may ultimately improve the care of patients with resistant BRAF-mutant melanoma by specifying tailored targeted combinations to overcome specific resistance mechanisms. (C) 2013 AACR. C1 [Wagle, Nikhil; Van Allen, Eliezer M.; Treacy, Daniel J.; Goetz, Eva M.; Hodis, Eran; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wagle, Nikhil; Van Allen, Eliezer M.; Garraway, Levi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Frederick, Dennie T.; Cooper, Zachary A.; Sullivan, Ryan J.; Lawrence, Donald P.; Getz, Gad; Flaherty, Keith T.; Wargo, Jennifer A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Wagle, Nikhil; Van Allen, Eliezer M.; Taylor-Weiner, Amaro; Rosenberg, Mara; Farlow, Deborah N.; Friedrich, Dennis C.; Anderka, Kristin; Perrin, Danielle; Johannessen, Cory M.; McKenna, Aaron; Cibulskis, Kristian; Kryukov, Gregory; Hodis, Eran; Fisher, Sheila; Getz, Gad; Gabriel, Stacey B.; Carter, Scott L.; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Hodis, Eran] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D1542, Boston, MA 02215 USA. EM jwargo@mdanderson.org; levi_garraway@dfci.harvard.edu RI Kryukov, Gregory/A-9592-2008; OI Cooper, Zachary/0000-0003-1059-0940 FU Conquer Cancer Foundation; Dana-Farber Leadership Council; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Melanoma Research Alliance; Starr Cancer Consortium; National Human Genome Research Institute [5U54HG003067-11]; National Cancer Institute [P01 CA163222 01A1, P50CA93683] FX This work was supported by the Conquer Cancer Foundation (to N. Wagle and E. M. Van Allen), the Dana-Farber Leadership Council (to E. M. Van Allen), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to K. T. Flaherty and L. A. Garraway), the Melanoma Research Alliance (to L. A. Garraway), the Starr Cancer Consortium (to L. A. Garraway), the National Human Genome Research Institute 5U54HG003067-11 (to G. Getz, S. B. Gabriel, and L. A. Garraway), and the National Cancer Institute P01 CA163222 01A1 and P50CA93683 (to L. A. Garraway). NR 24 TC 142 Z9 145 U1 1 U2 30 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2014 VL 4 IS 1 BP 61 EP 68 DI 10.1158/2159-8290.CD-13-0631 PG 8 WC Oncology SC Oncology GA 285ZP UT WOS:000329434300024 PM 24265154 ER PT J AU Van Allen, EM Wagle, N Sucker, A Treacy, DJ Johannessen, CM Goetz, EM Place, CS Taylor-Weiner, A Whittaker, S Kryukov, GV Hodis, E Rosenberg, M McKenna, A Cibulskis, K Farlow, D Zimmer, L Hillen, U Gutzmer, R Goldinger, SM Ugurel, S Gogas, HJ Egberts, F Berking, C Trefzer, U Loquai, C Weide, B Hassel, JC Gabriel, SB Carter, SL Getz, G Garraway, LA Schadendorf, D AF Van Allen, Eliezer M. Wagle, Nikhil Sucker, Antje Treacy, Daniel J. Johannessen, Cory M. Goetz, Eva M. Place, Chelsea S. Taylor-Weiner, Amaro Whittaker, Steven Kryukov, Gregory V. Hodis, Eran Rosenberg, Mara McKenna, Aaron Cibulskis, Kristian Farlow, Deborah Zimmer, Lisa Hillen, Uwe Gutzmer, Ralf Goldinger, Simone M. Ugurel, Selma Gogas, Helen J. Egberts, Friederike Berking, Carola Trefzer, Uwe Loquai, Carmen Weide, Benjamin Hassel, Jessica C. Gabriel, Stacey B. Carter, Scott L. Getz, Gad Garraway, Levi A. Schadendorf, Dirk CA Dermatologic Cooperative Oncology TI The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma SO CANCER DISCOVERY LA English DT Article ID ACQUIRED-RESISTANCE; SEQUENCING DATA; CANCER GENOME; BRAF; MUTATIONS; MEK; VEMURAFENIB; TUMOR; SURVIVAL; REVEALS AB Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAF(V600)-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a "long tail" of new mitogen-activated protein kinase (MAPK) pathway alterations (MAP2K2, MITF) that confer RAF inhibitor resistance. In three cases, multiple resistance gene alterations were observed within the same tumor biopsy. Overall, RAF inhibitor therapy leads to diverse clinical genetic resistance mechanisms, mostly involving MAPK pathway reactivation. Novel therapeutic combinations may be needed to achieve durable clinical control of BRAF(V600)-mutant melanoma. Integrating clinical genomics with preclinical screens may model subsequent resistance studies. SIGNIFICANCE: The use of RAF inhibitors for BRAF(V600)-mutant metastatic melanoma improves patient outcomes, but most patients demonstrate early or acquired resistance to this targeted therapy. We reveal the genetic landscape of clinical resistance mechanisms to RAF inhibitors from patients using whole-exome sequencing, and experimentally assess new observed mechanisms to define potential subsequent treatment strategies. (C)2013 AACR. C1 [Van Allen, Eliezer M.; Wagle, Nikhil; Treacy, Daniel J.; Goetz, Eva M.; Place, Chelsea S.; Hodis, Eran; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA USA. [Van Allen, Eliezer M.; Wagle, Nikhil; Johannessen, Cory M.; Place, Chelsea S.; Taylor-Weiner, Amaro; Whittaker, Steven; Kryukov, Gregory V.; Hodis, Eran; Rosenberg, Mara; McKenna, Aaron; Cibulskis, Kristian; Farlow, Deborah; Gabriel, Stacey B.; Carter, Scott L.; Getz, Gad; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hodis, Eran] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sucker, Antje; Zimmer, Lisa; Hillen, Uwe; Schadendorf, Dirk] Univ Duisburg Essen, West German Canc Ctr, Dept Dermatol, Univ Hosp, Essen, Germany. [Sucker, Antje; Zimmer, Lisa; Hillen, Uwe; Berking, Carola; Trefzer, Uwe; Loquai, Carmen; Weide, Benjamin; Hassel, Jessica C.; Schadendorf, Dirk] German Canc Consortium DKTK, Heidelberg, Germany. [Hassel, Jessica C.] Univ Heidelberg Hosp, Dept Dermatol, Heidelberg, Germany. [Gutzmer, Ralf] Hannover Med Sch, Dept Dermatol & Allergy, Hannover, Germany. [Ugurel, Selma] Univ Wurzburg, Dept Dermatol, Wurzburg, Germany. [Egberts, Friederike] Univ Schleswig Holstein Hosp, Dept Dermatol Venerol & Allergol, Kiel, Germany. [Berking, Carola] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. [Trefzer, Uwe] Humboldt Univ, Charite Univ Med Berlin, Dept Dermatol Venerol & Allergy, D-10099 Berlin, Germany. [Loquai, Carmen] Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55122 Mainz, Germany. [Weide, Benjamin] Univ Tubingen, Univ Med Ctr, Tubingen, Germany. [McKenna, Aaron] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Goldinger, Simone M.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Gogas, Helen J.] Univ Athens, Sch Med, Dept Med 1, GR-11527 Athens, Greece. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D1542, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu; dirk.schadendorf@uk-essen.de RI Kryukov, Gregory/A-9592-2008; Weide, Benjamin/N-3698-2013 FU National Cancer Institute [P01 CA163222 01A1, P50 CA 93683]; National Human Genome Research Institute [5U54HG003067-11]; Melanoma Research Alliance; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Harvard Clinical and Translational Science Center NIH [UL1 RR 025758]; National Institute of General Medical Sciences [T32GM07753]; Conquer Cancer Foundation; Dana-Farber Leadership Council; American Cancer Society FX This work was supported by the National Cancer Institute (Award #P01 CA163222 01A1, P50 CA 93683; to L. A. Garraway), National Human Genome Research Institute (Award #5U54HG003067-11; to L. A. Garraway, G. Getz, and S. B. Gabriel), the Melanoma Research Alliance (to L. A. Garraway), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to L. A. Garraway), the Harvard Clinical and Translational Science Center NIH Training Grant Award (Award #UL1 RR 025758; to C. S. Place), the National Institute of General Medical Sciences Grant T32GM07753 (to E. Hodis), the Conquer Cancer Foundation (to E. M. Van Allen and N. Wagle), the Dana-Farber Leadership Council (to E. M. Van Allen), and the American Cancer Society (to E.M. Van Allen). NR 52 TC 218 Z9 219 U1 3 U2 39 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2014 VL 4 IS 1 BP 94 EP 109 DI 10.1158/2159-8290.CD-13-0617 PG 16 WC Oncology SC Oncology GA 285ZP UT WOS:000329434300027 PM 24265153 ER PT J AU Bandeali, SJ Daye, J Virani, SS AF Bandeali, Salman J. Daye, Jad Virani, Salim S. TI Novel Therapies for Treating Familial Hypercholesterolemia SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Familial hypercholesterolemia; Mipomersen; Proprotein convertase subtilisin/kexin 9 inhibitors; Lomitapide ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; B SYNTHESIS INHIBITOR; VIVO GENE-THERAPY; TRIGLYCERIDE TRANSFER PROTEIN; PLACEBO-CONTROLLED TRIAL; MONOCLONAL-ANTIBODY; LDL CHOLESTEROL; DOUBLE-BLIND; PLASMA-CHOLESTEROL AB Familial hypercholesterolemia is an inherited disorder associated with early accelerated atherosclerosis with morbidity and mortality resulting from premature cardiovascular disease. Affected individuals have extreme elevations in low-density lipoprotein cholesterol levels. Patients usually do not achieve target reductions in cholesterol levels with conventional antihyperlipidemic pharmacotherapy. This unmet need has resulted in the recent development and approval of novel therapies targeting different cholesterol pathways. This article briefly summarizes familial hypercholesterolemia and then discusses the newer pharmacotherapies available in the management of familial hypercholesterolemia. C1 [Bandeali, Salman J.] St Lukes Episcopal Hosp, Texas Heart Inst, Cardiol Sect, Dept Med, Houston, TX 77030 USA. [Daye, Jad; Virani, Salim S.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Virani, Salim S.] Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA. [Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Virani, Salim S.] Houston Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX 77030 USA. [Virani, Salim S.] Michael E DeBakey VA Med Ctr, Cardiol Sect, Houston, TX 77030 USA. [Virani, Salim S.] Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev 152, Houston, TX 77030 USA. RP Virani, SS (reprint author), Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM salmanbandeali@hotmail.com; eldaye@bcm.edu; virani@bcm.edu FU Department of Veterans Affairs Health Services Research and Development Service Career Development Award FX Salim S. Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service Career Development Award. NR 52 TC 2 Z9 2 U1 0 U2 3 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD JAN PY 2014 VL 16 IS 1 AR 382 DI 10.1007/s11883-013-0382-0 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 288LY UT WOS:000329614700006 PM 24293346 ER PT J AU Villani, V Milanesi, A Sedrakyan, S Da Sacco, S Angelow, S Conconi, MT Di Liddo, R De Filippo, R Perin, L AF Villani, Valentina Milanesi, Anna Sedrakyan, Sargis Da Sacco, Stefano Angelow, Susanne Conconi, Maria Teresa Di Liddo, Rosa De Filippo, Roger Perin, Laura TI Amniotic fluid stem cells prevent beta-cell injury SO CYTOTHERAPY LA English DT Article DE amniotic fluid; beta-cell; pancreas; regeneration; stem cells; type 1 diabetes mellitus ID INSULIN-PRODUCING CELLS; TYPE-1 DIABETES-MELLITUS; BONE-MARROW; IN-VITRO; VASCULAR MATURATION; PANCREATIC-ISLETS; GENE-EXPRESSION; DIFFERENTIATION; MICE; PROLIFERATION AB Background aims. The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating beta-cell injury and restoring beta-cell function. Methods. Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation. Results. AFSC injection resulted in protection from beta-cell damage and increased beta-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, beta-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining beta-cell mass and function. Conclusions. Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous beta-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non-genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved. C1 [Villani, Valentina; Sedrakyan, Sargis; Da Sacco, Stefano; Angelow, Susanne; De Filippo, Roger; Perin, Laura] Univ So Calif, Childrens Hosp Los Angeles, Dept Urol, Los Angeles, CA USA. [Milanesi, Anna] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA USA. [Conconi, Maria Teresa; Di Liddo, Rosa] Univ Padua, Dept Pharmaceut Sci, Padua, Italy. RP Perin, L (reprint author), Childrens Hosp Los Angeles, Dept Urol, 4661 Sunset Blvd,Mailstop 35, Los Angeles, CA 90027 USA. EM lperin@chla.usc.edu FU Fondazione Ing Aldo Gini (University of Padua); Iacocca foundation; GOFARR FX We thank Fondazione Ing Aldo Gini (University of Padua) for funding support to the present research. We also would like to thank Dr Habibian for providing the human amniotic fluid samples. This work was supported by The Iacocca foundation and GOFARR. NR 46 TC 4 Z9 4 U1 2 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD JAN PY 2014 VL 16 IS 1 BP 41 EP 55 DI 10.1016/j.jcyt.2013.08.010 PG 15 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 288DS UT WOS:000329592800005 PM 24210784 ER PT J AU Rabelo, DR Rocha, MOD de Barros, MVL da Silva, JLP Tan, TC Nunes, MCP AF Rabelo, Daniel R. da Costa Rocha, Manoel Otavio de Barros, Marcio V. L. Padilha da Silva, Jose Luiz Tan, Timothy C. Nunes, Maria C. P. TI Impaired Coronary Flow Reserve in Patients with Indeterminate Form of Chagas' Disease SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE coronary flow reserve; transthoracic dipyridamole stress echocardiography; Chagas' disease; heart rate recovery ID TRANSTHORACIC DOPPLER-ECHOCARDIOGRAPHY; NONISCHEMIC DILATED CARDIOMYOPATHY; NONINVASIVE ASSESSMENT; VELOCITY RESERVE; ARTERY-STENOSIS; DYSFUNCTION; CARDIOPATHY AB BackgroundPrevious studies suggest that microvascular abnormalities may contribute to the pathogenesis of Chagas' heart disease. Coronary flow reserve (CFR) expressed by the maximum achievable flow relative to baseline flow in the coronary microcirculation, may be useful in identifying patients who may be developing cardiac manifestations of the disease. This study aims to assess the CFR in patients with indeterminate form of Chagas' disease, and also to identify the determinants of CFR. MethodsSixty-four asymptomatic patients (37% male; age 49.911.5years) with normal cardiovascular exams classified as in indeterminate form of Chagas' disease underwent transthoracic dipyridamole (0.84mg/kg in 6min) stress echocardiography, and were compared with a control group of healthy patients. Coronary flow reserve was assessed on left anterior descending artery using pulsed Doppler as the ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. A treadmill exercise test was performed to rule out ischemia. ResultsAll patients had good functional capacity assessed by exercise testing with peak oxygen consumption (VO2) of 28 +/- 11mL/kg per minute, similar to the controls. There were no differences in the echocardiographic parameters of diastolic and systolic left ventricular function and right ventricular function between the patients and controls. Coronary flow reserve was significantly lower in Chagas' disease patients than those in healthy individuals (1.9 +/- 0.4 vs. 2.6 +/- 0.5; P<0.001). Several factors were correlated with the CFR, including age, ejection fraction, left ventricular diastolic function, heart rate recovery, and the presence of Chagas' disease. In a multivariate analysis, age and positive serology for Chagas' disease were independent factors associated with the CFR. ConclusionsCoronary flow reserve was impaired in Chagas' disease patients in the indeterminate form compared with healthy individuals with similar clinical features. Among all variables tested, age and positive serology for Chagas' disease were independent factors associated with the CFR. C1 [Rabelo, Daniel R.; da Costa Rocha, Manoel Otavio; de Barros, Marcio V. L.; Nunes, Maria C. P.] Univ Fed Minas Gerais, Sch Med, Postgrad Program Infect Dis & Trop Med, Belo Horizonte, MG, Brazil. [Padilha da Silva, Jose Luiz] Univ Fed Minas Gerais, Dept Stat, Belo Horizonte, MG, Brazil. [Tan, Timothy C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Nunes, MCP (reprint author), Univ Fed Minas Gerais, Dept Clin Med, Av Prof Alfredo Balena 190, BR-34099437 Belo Horizonte, MG, Brazil. EM mcarmo@waymail.com.br FU CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brasilia, Brazil); FAPEMIG (Fundacao de Apoio a Pesquisa do Estado de Minas Gerais, BH, MG, Brazil) FX CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brasilia, Brazil), and FAPEMIG (Fundacao de Apoio a Pesquisa do Estado de Minas Gerais, BH, MG, Brazil). NR 25 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 EI 1540-8175 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2014 VL 31 IS 1 BP 67 EP 73 DI 10.1111/echo.12364 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 282TS UT WOS:000329197100021 PM 24103102 ER PT J AU Quinn, LS Anderson, BG Conner, JD Wolden-Hanson, T Marcell, TJ AF Quinn, LeBris S. Anderson, Barbara G. Conner, Jennifer D. Wolden-Hanson, Tami Marcell, Taylor J. TI IL-15 Is Required for Postexercise Induction of the Pro-Oxidative Mediators PPAR delta and SIRT1 in Male Mice SO ENDOCRINOLOGY LA English DT Article ID HUMAN SKELETAL-MUSCLE; ENDURANCE EXERCISE; GENE-EXPRESSION; INTERLEUKIN-15; RECEPTOR; PGC-1-ALPHA; PROTEIN; FAT; MASS; OVEREXPRESSION AB Physical exercise induces transient upregulation of the pro-oxidative mediators peroxisome proliferator-activated receptor-delta (PPAR delta), silent information regulator of transcription (sirtuin)-1 (SIRT1), PPAR gamma coactivator 1 alpha (PGC-1 alpha), and PGC-1 beta in skeletal muscle. To determine the role of the cytokine IL-15 in acute postexercise induction of these molecules, expression of these factors after a bout of exhaustive treadmill running was examined in the gastrocnemius muscle of untrained control and IL-15-knockout (KO) mice. Circulating IL-15 levels increased transiently in control mice after exercise. Control mice, but not IL-15-KO mice, upregulated muscle PPAR delta and SIRT1 protein after exercise, accompanied by a complex pattern of mRNA expression for these factors. However, in exhaustive exercise, control mice ran significantly longer than IL-15-KO mice. Therefore, in a second experiment, mice were limited to a 20-minute run, after which a similar pattern of induction of muscle PPAR delta and SIRT1 protein by control mice only was observed. In a separate experiment, IL-15-KO mice injected systemically with recombinant IL-15 upregulated muscle PPAR delta and SIRT1 mRNA within 30 minutes and also exhibited increased muscle PPAR delta protein levels by 3 hours. After exercise, both control and IL-15-KO mice downregulated IL-15 receptor-alpha (IL-15R alpha) mRNA, whereas IL-15R alpha-deficient mice exhibited constitutively elevated circulating IL-15 levels. These observations indicate IL-15 release after exercise is necessary for induction of PPAR delta and SIRT1 at the protein level in muscle tissue and suggest that exercise releases IL-15 normally sequestered by the IL-15R alpha in the resting state. These findings could be used to develop an IL-15-based strategy to induce many of the metabolic benefits of physical exercise. C1 [Quinn, LeBris S.; Anderson, Barbara G.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Quinn, LeBris S.; Conner, Jennifer D.; Wolden-Hanson, Tami] VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. [Quinn, LeBris S.; Conner, Jennifer D.] Seattle Inst Biomed & Clin Res, Seattle, WA 98108 USA. [Quinn, LeBris S.; Anderson, Barbara G.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA. [Marcell, Taylor J.] Calif State Univ Stanislaus, Dept Kinesiol, Turlock, CA 95382 USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM quinnL@uw.edu FU Department of Veterans Affairs [BX001026] FX This work was supported by Merit Review BX001026 from the Department of Veterans Affairs (to L. S. Q.) and use of resources and facilities including the Rodent Metabolic and Behavioral Phenotyping Core at VA Puget Sound Health Care System, the Transgenic Resource Core at the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIA 5P30AG-013280), and the University of Washington Diabetes Endocrinology Research Center (NIH P30 DK-17047). NR 45 TC 12 Z9 12 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2014 VL 155 IS 1 BP 143 EP 155 DI 10.1210/en.2013-1645 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 279NU UT WOS:000328967500020 PM 24169546 ER PT J AU Singh, JP Kandala, J Camm, AJ AF Singh, Jagmeet P. Kandala, Jagdesh Camm, A. John TI Non-pharmacological modulation of the autonomic tone to treat heart failure SO EUROPEAN HEART JOURNAL LA English DT Review DE Autonomic nervous system; Sympathetic nervous system; Parasympathetic nervous system; Renal denervation; Vagal nerve stimulator; Carotid baroreceptor stimulation; Heart rate variability; Baroreflex sensitivity; Spinal cord stimulation ID RENAL SYMPATHETIC DENERVATION; VAGUS NERVE-STIMULATION; BAROREFLEX ACTIVATION THERAPY; SPINAL-CORD STIMULATION; CARDIAC RESYNCHRONIZATION THERAPY; ACUTE MYOCARDIAL-INFARCTION; RHEOS PIVOTAL TRIAL; RESISTANT HYPERTENSION; RATE-VARIABILITY; BLOOD-PRESSURE AB The autonomic nervous system has a significant role in the pathophysiology and progression of heart failure. The absence of any recent breakthrough advances in the medical therapy of heart failure has led to the evolution of innovative non-pharmacological interventions that can favourably modulate the cardiac autonomic tone. Several new therapeutic modalities that may act at different levels of the autonomic nervous system are being investigated for their role in the treatment of heart failure. The current review examines the role of renal denervation, vagal nerve stimulators, carotid baroreceptors, and spinal cord stimulators in the treatment of heart failure. C1 [Singh, Jagmeet P.; Kandala, Jagdesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Div Cardiol,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Camm, A. John] St Georges Univ London, Dept Clin Sci, London, England. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Div Cardiol,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM jsingh@partners.org FU St Jude Medical; Medtronic Inc.; Boston Scientific Corp.; Biotronik; Medtronic; Sorin Group FX J.P.S. reports receiving research grants from St Jude Medical, Medtronic Inc., Boston Scientific Corp. and Biotronik, consulting from Boston Scientific Corp., Medtronic Inc, Sorin Group, St Jude Medical, Biosense Webster and receiving lecture fees from Boston Scientific Corp., Medtronic, St Jude Medical and Sorin Group. JK & AJC: none relevant to this article. NR 95 TC 21 Z9 22 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2014 VL 35 IS 2 BP 77 EP + DI 10.1093/eurheartj/eht436 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 291QU UT WOS:000329844900009 PM 24174128 ER PT J AU Quick, V Lipsky, LM Laffel, LMB Mehta, SN Quinn, H Nansel, TR AF Quick, V. Lipsky, L. M. Laffel, L. M. B. Mehta, S. N. Quinn, H. Nansel, T. R. TI Relationships of neophobia and pickiness with dietary variety, dietary quality and diabetes management adherence in youth with type 1 diabetes SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary variety; dietary quality; neophobia; pickiness; type 1 diabetes; youth ID CHILDRENS FOOD PREFERENCES; CORONARY-HEART-DISEASE; BODY-MASS INDEX; CHILDHOOD; ADOLESCENTS; ACCEPTANCE; CONSUMPTION; VALIDATION; ADULTS; PREDICTORS AB BACKGROUND/OBJECTIVES: Neophobia, pickiness and diet variety are associated with diet quality and health outcomes in young children. Limited research has examined these associations among youth with type 1 diabetes (T1D), a population at risk for poor health outcomes when dietary quality is inadequate. SUBJECTS/METHODS: Youth (n = 252, age 13.2 +/- 2.8 years, 92% white, diabetes duration 6.3 +/- 3.4 years) with T1D and their parents completed 3-day youth diet records; parents completed questionnaires regarding youth neophobia, pickiness and diabetes management adherence. Medical records provided biomedical data. Dietary quality indicators included Nutrient-Rich Foods Index 9.3 (NRF9.3), Healthy Eating Index-2005 (HEI-2005), Whole Plant Food Density (WPFD) and key single nutrients. Dietary variety was operationalized as a count of 20 recommended food groups consumed. Relationships of dietary quality and diabetes management adherence with neophobia, pickiness and dietary variety as independent variables were examined using multiple linear regression analyses adjusted for total energy intake, age, height and weight. RESULTS: In multiple linear regression analyses, NRF9.3 and HEI-2005 were each inversely associated with neophobia and pickiness, and positively associated with dietary variety. WPF and potassium were each positively associated and saturated fat was inversely associated with dietary variety. However, in models simultaneously including neophobia, pickiness and dietary variety as independent correlates of dietary quality, only relationships with dietary variety remained significant. Diabetes management adherence was negatively associated with both neophobia and pickiness and positively associated with dietary variety. CONCLUSIONS: Findings suggest that increasing dietary variety may contribute toward improved dietary quality among youth with T1D, despite potentially adverse influences of neophobia and pickiness. C1 [Quick, V.; Lipsky, L. M.; Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Laffel, L. M. B.; Mehta, S. N.; Quinn, H.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect,Pediat Adolescent & Young, Boston, MA 02115 USA. RP Quick, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, US Dept HHS, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM gingermquick@gmail.com OI Quick, Virginia/0000-0002-4338-963X; Nansel, Tonja/0000-0002-8298-7595 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Contract Number HHSN267200703434C. NR 49 TC 5 Z9 5 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 EI 1476-5640 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD JAN PY 2014 VL 68 IS 1 BP 131 EP 136 DI 10.1038/ejcn.2013.239 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 285ZL UT WOS:000329433900024 PM 24253761 ER PT J AU Nishino, M Itoh, H Hatabu, H AF Nishino, Mizuki Itoh, Harumi Hatabu, Hiroto TI A practical approach to high-resolution CT of diffuse disease? SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE CT; High-resolution CT; Diffuse lung disease; Interstitial lung disease; Lung ID NONSPECIFIC INTERSTITIAL PNEUMONIA; IDIOPATHIC PULMONARY-FIBROSIS; THIN-SECTION CT; LANGERHANS CELL HISTIOCYTOSIS; RESPIRATORY BRONCHIOLITIS; LUNG-DISEASE; CLINICAL-SIGNIFICANCE; LYMPHANGIOLEIOMYOMATOSIS; FEATURES; SPECTRUM AB Diffuse lung disease presents a variety of high-resolution CT findings reflecting its complex pathology, and provides diagnostic challenge to radiologists. Frequent modification of detailed pathological classification makes it difficult to keep up with the latest understanding. In this review, we describe a practical approach to high-resolution CT diagnosis of diffuse lung disease, emphasizing (1) analysis of "distribution" of the abnormalities, (2) interpretation of "pattern" in relation to distribution, (3) utilization of associated imaging findings and clinical information, and (4) chronicity of the findings. This practical approach will help radiologists establish a way to interpret high-resolution CT, leading to pin-point diagnosis or narrower differential diagnoses of diffuse lung diseases. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Nishino, Mizuki] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Nishino, Mizuki] Brigham & Womens Hosp, Boston, MA 02215 USA. [Itoh, Harumi] Univ Fukui, Fac Med Sci, Dept Radiol, Matsuoka, Fukui, Japan. [Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@DFCI.HARVARD.EDU FU National Institutes of Health [1K23CA157631-01A1, 5R21 CA11627-02] FX The investigators were supported by 1K23CA157631-01A1 (NCI) (M.N.), and 5R21 CA11627-02 (H.H.) from the National Institutes of Health. NR 37 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD JAN PY 2014 VL 83 IS 1 BP 6 EP 19 DI 10.1016/j.ejrad.2013.12.028 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285YC UT WOS:000329429900013 PM 23410907 ER PT J AU Sibila, O Mortensen, EM Anzueto, A Laserna, E Restrepo, MI AF Sibila, Oriol Mortensen, Eric M. Anzueto, Antonio Laserna, Elena Restrepo, Marcos I. TI Prior cardiovascular disease increases long-term mortality in COPD patients with pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; ACUTE CORONARY SYNDROMES; UNITED-STATES; CARE; HOSPITALIZATIONS; COMORBIDITY; INFECTION; PATTERNS; OUTCOMES AB There is controversy regarding the impact of chronic obstructive pulmonary disease (COPD) in clinical outcomes in elderly patients with pneumonia. Comorbidities such as cardiovascular disease have been reported to play an important role in patients with acute exacerbations of COPD. However, limited data are available regarding the impact of cardiovascular disease in elderly COPD patients who require hospitalisation for pneumonia. We examined a cohort of subjects with pneumonia and pre-existing COPD. Prior cardiovascular disease was defined as history of myocardial infarction, congestive heart failure, cardiac arrhythmia, unstable angina or stroke. Outcomes examined included 30-day, 90-day, 6-month and 1-year mortality. We included 17 140 elderly COPD patients who were hospitalised for pneumonia. Prior cardiovascular disease was present in 10 240 (59.7%) patients. Prior cardiovascular disease was independently associated with 90-day mortality (21.3% versus 19.4%; hazard ratio (HR) 1.29, 95% CI 1.02-1.17), 6-month mortality (29.0% versus 26.1%; HR 1.28, 95% CI 1.07-1.50) and 12-month mortality (39.2% versus 34.5%; HR 1.33, 95% CI 1.15-1.54) when compared to no prior cardiovascular disease. The temporal differential effect between groups increases from 1.0% at 30 days to 4.7% at 1 year. Prior cardiovascular disease is associated with increased long-term mortality in elderly COPD patients with pneumonia. Differences in mortality rates increased over time. C1 [Sibila, Oriol; Anzueto, Antonio; Laserna, Elena; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Vet Affairs North Texas Hlth Care Syst, San Antonio, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Anzueto, Antonio; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Laserna, Elena] Hosp Comarcal Mollet, Mollet Del Valles, Spain. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst ALMD, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Howard Hughes Medical Institute faculty-start up grant [00378-001]; Dept of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant; Instituto de Salud Carlos III [BAE11/00102]; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia (SOCAP); Fundacio Catalana de Pneumologia (FUCAP); National Heart, Lung, and Blood Institute [K23HL096054] FX This research was supported by Howard Hughes Medical Institute faculty-start up grant 00378-001 and a Dept of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant. O. Sibila is supported by Instituto de Salud Carlos III (BAE11/00102). O. Sibila and E. Laserna are supported by Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Societat Catalana de Pneumologia (SOCAP) and Fundacio Catalana de Pneumologia (FUCAP). M.I. Restrepo's time is partially protected by Award Number K23HL096054 from the National Heart, Lung, and Blood Institute. The funding agencies had no role in the preparation, review, or approval of the manuscript. The views expressed in this article are those of the author and do not necessarily represent the views of the Dept of Veterans Affairs. NR 31 TC 7 Z9 7 U1 0 U2 4 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD JAN PY 2014 VL 43 IS 1 BP 36 EP 42 DI 10.1183/09031936.00117312 PG 7 WC Respiratory System SC Respiratory System GA 287ON UT WOS:000329552200009 PM 23598950 ER PT J AU Brown, CM Cronholm, PF Wright, J Warning, WJ Radosh, L Gabbay, R AF Brown, Carina M. Cronholm, Peter F. Wright, Jessica Warning, William J., II Radosh, Lee Gabbay, Robert TI A Collaborative Approach to Achieving NCQA PCMH Recognition Within Family Medicine Residency Practices SO FAMILY MEDICINE LA English DT Article ID CARE; HOME; EDUCATION; LESSONS AB BACKGROUND AND OBJECTIVES: The Pennsylvania Academy of Family Physicians (PAFP) developed a statewide Residency Program Collaborative (RPC) to facilitate family medicine residency practices in Pennsylvania becoming recognized patient-centered medical homes (PCMHs). This report outlines the methods and a brief evaluation of the RPC, which included 20 residency practices. Participants attended tri-annual learning sessions and monthly conference calls, received physician faculty mentorship, and reported clinical quality data monthly on diabetes and ischemic vascular disease. METHODS: Two years after the start of the RPC, surveys were sent to residents, staff, providers, and administrators at participating practices to measure attendance and usefulness of collaborative sessions, mentors, and monthly reports. Evaluators also mapped the RPC curriculum to the Accreditation Council of Graduate Medical Education (ACGME) Core Competencies. RESULTS: All 20 participating practices achieved National Committee for Quality Assurance (NCQA) PCMH recognition, with 17 attaining Level 3 recognition. A total of 295 surveys were collected (92 residents, 71 faculty, and 132 office staff/administrators). Survey data showed higher collaborative attendance for residents and faculty compared to office staff/administrators (similar to 84% versus 45%). No differences were noted between resident and faculty respondents regarding perceived helpfulness of collaborative sessions (6.3 and 6.5, respectively), mentors (6.6 and 6.2) and monthly reports (6.4 and 6.5), with both groups rating these components more highly than staff/administrators (5.3, 5.3, and 5.4 for each category). CONCLUSIONS: Learning collaboratives can assist residency practices in achieving PCMH recognition while concurrently providing an educational framework aligned with residency program Core Competencies. The RPC intervention, including learning sessions, monthly conference calls, data reporting, and faculty mentors, also can effectively guide residency practices in the PCMH transformation process and can serve as a means to experientially imbue future family physicians with the attitudes and skills to create and effectively operate their practices under PCMH principles. C1 [Brown, Carina M.] Univ Penn, Penn State Coll Med, Springfield, PA USA. [Cronholm, Peter F.] Univ Penn, Dept Family Med & Community Hlth, Springfield, PA USA. [Wright, Jessica] Penn State Hershey Diabet Inst, Springfield, PA USA. [Warning, William J., II] Crozer Keystone Family Med Residency Program, Springfield, PA USA. [Radosh, Lee] Reading Hosp Med Ctr, W Reading, PA USA. [Gabbay, Robert] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Gabbay, R (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl,Room 267, Boston, MA 02215 USA. EM robert.gabbay@joslin.harvard.edu FU The Pennsylvania Academy of Family Physicians (PAFP) FX The Pennsylvania Academy of Family Physicians (PAFP) provided support for this work. NR 25 TC 2 Z9 2 U1 1 U2 4 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 EI 1938-3800 J9 FAM MED JI Fam. Med. PD JAN PY 2014 VL 46 IS 1 BP 19 EP 27 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 289LJ UT WOS:000329683700004 PM 24415504 ER PT J AU Thomas, S Wright, KJ Le Corre, S Micalizzi, A Romani, M Abhyankar, A Saada, J Perrault, I Amiel, J Litzler, J Filhol, E Elkhartoufi, N Kwong, M Casanova, JL Boddaert, N Baehr, W Lyonnet, S Munnich, A Burglen, L Chassaing, N Encha-Ravazi, F Vekemans, M Gleeson, JG Valente, EM Jackson, PK Drummond, IA Saunier, S Attie-Bitach, T AF Thomas, Sophie Wright, Kevin J. Le Corre, Stephanie Micalizzi, Alessia Romani, Marta Abhyankar, Avinash Saada, Julien Perrault, Isabelle Amiel, Jeanne Litzler, Julie Filhol, Emilie Elkhartoufi, Nadia Kwong, Mandy Casanova, Jean-Laurent Boddaert, Nathalie Baehr, Wolfgang Lyonnet, Stanislas Munnich, Arnold Burglen, Lydie Chassaing, Nicolas Encha-Ravazi, Ferechte Vekemans, Michel Gleeson, Joseph G. Valente, Enza Maria Jackson, Peter K. Drummond, Iain A. Saunier, Sophie Attie-Bitach, Tania TI A Homozygous PDE6D Mutation in Joubert Syndrome Impairs Targeting of Farnesylated INPP5E Protein to the Primary Cilium SO HUMAN MUTATION LA English DT Article DE Joubert syndrome; primary cilia; PDE6D; INPP5E; prenylation ID CYCLIC-GMP PHOSPHODIESTERASE; SEQUENCING-BASED DISCOVERY; PRENYL-BINDING PROTEIN; DELTA-SUBUNIT; DEFICIENCY; ZEBRAFISH; CILIOPATHIES; TRANSPORT; ARL2-GTP; IMMUNITY AB Joubert syndrome (JS) is characterized by a distinctive cerebellar structural defect, namely the << molar tooth sign >>. JS is genetically heterogeneous, involving 20 genes identified to date, which are all required for cilia biogenesis and/or function. In a consanguineous family with JS associated with optic nerve coloboma, kidney hypoplasia, and polydactyly, combined exome sequencing and mapping identified a homozygous splice-site mutation in PDE6D, encoding a prenyl-binding protein. We found that pde6d depletion in zebrafish leads to renal and retinal developmental anomalies and wild-type but not mutant PDE6D is able to rescue this phenotype. Proteomic analysis identified INPP5E, whose mutations also lead to JS or mental retardation, obesity, congenital retinal dystrophy, and micropenis syndromes, as novel prenyl-dependent cargo of PDE6D. Mutant PDE6D shows reduced binding to INPP5E, which fails to localize to primary cilia in patient fibroblasts and tissues. Furthermore, mutant PDE6D is unable to bind to GTP-bound ARL3, which acts as a cargo-release factor for PDE6D-bound INPP5E. Altogether, these results indicate that PDE6D is required for INPP5E ciliary targeting and suggest a broader role for PDE6D in targeting other prenylated proteins to the cilia. This study identifies PDE6D as a novel JS disease gene and provides the first evidence of prenyl-binding-dependent trafficking in ciliopathies. C1 [Thomas, Sophie; Perrault, Isabelle; Amiel, Jeanne; Lyonnet, Stanislas; Munnich, Arnold; Encha-Ravazi, Ferechte; Vekemans, Michel; Attie-Bitach, Tania] Hop Necker Enfants Malad, INSERM, U781, F-75743 Paris 15, France. [Thomas, Sophie; Perrault, Isabelle; Amiel, Jeanne; Filhol, Emilie; Casanova, Jean-Laurent; Boddaert, Nathalie; Lyonnet, Stanislas; Munnich, Arnold; Encha-Ravazi, Ferechte; Vekemans, Michel; Saunier, Sophie; Attie-Bitach, Tania] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, Paris, France. [Wright, Kevin J.; Kwong, Mandy; Jackson, Peter K.] Genentech Inc, San Francisco, CA 94080 USA. [Le Corre, Stephanie; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA. [Micalizzi, Alessia] Univ Messina, Dept Med & Surg Paediat Sci, Messina, Italy. [Abhyankar, Avinash; Casanova, Jean-Laurent] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA. [Saada, Julien] Hop Antoine Beclere, AP HP, Serv Gynecol Obstet, Clamart, France. [Amiel, Jeanne; Litzler, Julie; Elkhartoufi, Nadia; Lyonnet, Stanislas; Munnich, Arnold; Encha-Ravazi, Ferechte; Vekemans, Michel; Attie-Bitach, Tania] Hop Necker Enfants Malad, AP HP, Dept Genet, F-75743 Paris 15, France. [Filhol, Emilie; Saunier, Sophie] Hop Necker Enfants Malad, INSERM, U983, Paris, France. [Casanova, Jean-Laurent] Necker Med Sch, INSERM, U980, Lab Human Genet Infect Dis, Paris, France. [Boddaert, Nathalie] Hop Necker Enfants Malad, AP HP, Serv Radiol Pediat, F-75743 Paris 15, France. [Baehr, Wolfgang] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84132 USA. [Burglen, Lydie] Hop Trousseau, AP HP, Ctr Reference Malformat & Malad Congenitales Cerv, F-75012 Paris, France. [Burglen, Lydie] Serv Genet, F-75012 Paris, France. [Chassaing, Nicolas] CHU Toulouse, UPSIII EA 4555, Serv Genet Med, Toulouse, France. [Gleeson, Joseph G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurosci & Pediat, Neurogenet Lab,Inst Genom Med, San Diego, CA 92103 USA. [Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Attie-Bitach, T (reprint author), Hop Necker Enfants Malad, Dept Genet, 149 Rue Sevres, F-75743 Paris 15, France. EM tania.attie@inserm.fr FU Agence Nationale de la Recherche [ANR 1122 01 FOETOCILPATH]; IMAGINE Institute; Fondation pour la Recherche Medicale [FRM DEQ20071210558]; National Institutes of Health [DK053093, DK070263, NS048453]; European Research Council (ERC) [260888]; Italian Ministry of Health FX Contract grant sponsors: Agence Nationale de la Recherche (ANR 1122 01 FOETOCILPATH); IMAGINE Institute; Fondation pour la Recherche Medicale (FRM DEQ20071210558); National Institutes of Health (DK053093, DK070263, NS048453); European Research Council (ERC Starting Grant 260888); The Italian Ministry of Health (Ricerca Corrente 2012 and Ricerca Finalizzata Malattie Rare 2008). NR 31 TC 40 Z9 43 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2014 VL 35 IS 1 BP 137 EP 146 DI 10.1002/humu.22470 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 289JP UT WOS:000329678600018 PM 24166846 ER PT J AU Sohn, K Lv, W Lee, KC Galea, AM Hirschman, GB Hayward, AM Cohen, RJ Armoundas, AA AF Sohn, Kwanghyun Lv, Wener Lee, Kichang Galea, Anna M. Hirschman, Gordon B. Hayward, Alison M. Cohen, Richard J. Armoundas, Antonis A. TI The Single Equivalent Moving Dipole Model Does Not Require Spatial Anatomical Information to Determine Cardiac Sources of Activation SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Ablation; body surface potentials; cardiac arrhythmias; catheter guiding; equivalent dipole ID RADIOFREQUENCY CATHETER ABLATION; VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION; ELECTRICAL ACTIVATION; MAPPING SYSTEM; TORSO MODEL; ELECTROPHYSIOLOGY; NONCONTACT; SITES; APPLICABILITY AB Radio-frequency catheter ablation (RCA) is an established treatment for ventricular tachycardia (VT). A key feature of the RCA procedure is the need for a mapping approach that facilitates the identification of the target ablation site. In this study, we investigate the effect of the location of the reference potential and spatial anatomical constraints on the accuracy of an algorithm to identify the target site for ablation therapy of VT. This algorithm involves processing body surface potentials using the single equivalent moving dipole (SEMD) model embedded in an infinite homogeneous volume conductor to model cardiac electrical activity. We employed a swine animal model and an electrode array of nine electrodes that was sutured on the epicardial surface of the right ventricle. We identified two potential reference electrode locations: at an electrode most far away from the heart (R1) and at the average of all 64 body surface electrode potentials (R2). Also, we developed three spatial "constraining" schemes of the algorithm used to obtain the SEMD location: one that does not impose any constraint on the inverse solution (S1), one that constrains the solution into a volume that corresponds to the heart (S2), and one that constrains the solution into a volume that corresponds to the body surface (S3). We have found that R2S1 is the most accurate approach (p < 0.05 versus R1S1 at earliest activation time-EAT) for localizing epicardial electrical sources of known locations in vivo. Although the homogeneous volume conductor introduces systematic error in the estimated compared to the true dipole location, we have observed that the overall error of the estimated interelectrode distance compared to the true one was 0.4 +/- 0.4 cm and 0.4 +/- 0.1 cm for the R1S1 and R2S1 combinations, respectively, at the EAT (p = N.S.) and 1.0 +/- 0.6 and 0.5 +/- 0.4 cm, respectively, at the pacing spike time (PST, p < 0.05). In conclusion, our algorithm to estimate the SEMD parameters from body surface potentials can potentially be a useful method to rapidly and accurately guide the catheter tip to the target site during a RCA procedure without the need for spatial anatomical information obtained by conventional imaging modalities. C1 [Sohn, Kwanghyun; Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Lv, Wener; Lee, Kichang; Cohen, Richard J.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Galea, Anna M.; Hirschman, Gordon B.] Vivonics Corp, Waltham, MA 02451 USA. [Hayward, Alison M.] Concord Biomed Sci & Emerging Technol Inc, Vet Serv, Lexington, MA 02421 USA. [Armoundas, Antonis A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sohn, K (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM ksohn@partners.org; lvwener@MIT.EDU; kclee@mit.edu; agalea@vivonics.com; ghirschman@vivonics.com; ahayward@cbset.org; rjcohen@mit.edu; aarmoundas@partners.org FU NIH [1RO1HL103961, 4 R44 H L079726-02] FX The work was supported by NIH under Grant 1RO1HL103961 and 4 R44 H L079726-02. K. Sohn and W. Lv are equally contributing authors. NR 30 TC 2 Z9 2 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD JAN PY 2014 VL 18 IS 1 BP 222 EP 230 DI 10.1109/JBHI.2013.2268012 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 287CM UT WOS:000329516400025 PM 24403420 ER PT J AU Drain, PK Mayeza, L Bartman, P Hurtado, R Moodley, P Varghese, S Maartens, G Alvarez, GG Wilson, D AF Drain, P. K. Mayeza, L. Bartman, P. Hurtado, R. Moodley, P. Varghese, S. Maartens, G. Alvarez, G. G. Wilson, D. TI Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; C-reactive protein; HIV/AIDS; point-of-care test; diagnostic testing; South Africa ID SMEAR-NEGATIVE TUBERCULOSIS; ANTIRETROVIRAL THERAPY; PULMONARY TUBERCULOSIS; CARE; ASSAY; IMPLEMENTATION; RESISTANCE; SETTINGS; CHILDREN; ADULTS AB OBJECTIVE: To determine the accuracy and role of rapid C-reactive protein (CRP) testing in human immunodeficiency virus (HIV) infected individuals with presumed tuberculosis (TB). DESIGN: We enrolled REV-infected adults (>= 18 years) with a cough of >= 2 weeks and negative sputum smears for acid-fast bacilli in KwaZulu-Natal, South Africa. Participants were evaluated for pulmonary TB (PTB) by a nurse with rapid CRP, and independently by a physician by chest radiograph. Rapid CRP test results were compared with laboratory CRP and sputum sent for confirmation of TB. RESULTS: Among 93 participants, 55 (59%) were female, the mean age was 35 years, and the median CD4 count was 177/mm(3). Forty-five (54%) participants were diagnosed with PTB. Diagnostic sensitivity and specificity were respectively 95% (95%CI 74-99) and 51% (95%CI 35-66) for rapid CRP >8 mg/l,87% (95%CI 73-96) and 53% (95 %CI 38-68) for nurse assessment, and 69% (95%CI 52-83) and 76% (95%CI 61-87) for physician examination. Combining a negative rapid CRP <= 8 mg/l) with nurse and physician assessments reduced the post-test probability of PTB from 22% to 6% and from 32% to 6%, respectively. CONCLUSION: Rapid CRP testing helped exclude PTB, and may be a valuable test in assisting nurses and physicians in TB-endemic regions. C1 [Drain, P. K.; Hurtado, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Mayeza, L.; Bartman, P.; Alvarez, G. G.; Wilson, D.] Univ KwaZulu Natal, Edendale Hosp, Dept Med, Edendale Hosp Res Unit, Pietermaritzburg, South Africa. [Moodley, P.] Univ KwaZulu Natal, Dept Med Microbiol, Durban, South Africa. [Varghese, S.] Ottawa Gen Hosp, Dept Med, Ottawa, ON K1H 8L6, Canada. [Maartens, G.] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,943, Boston, MA 02114 USA. EM pdrain@partners.org RI Maartens, Gary/F-3836-2014; OI Maartens, Gary/0000-0003-3080-6606; Drain, Paul/0000-0003-3300-3817 FU KwaZulu-Natal Department of Health; Howard Hughes Medical Institute, KwaZulu-Natal Research Initiative for Tuberculosis and HIV; Harvard Global Health Institute for Global Health, Cambridge, MA, USA; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University, Nashville, TN, USA [R24 TW007988] FX The authors acknowledge the support of the KwaZulu-Natal Department of Health. They appreciate the assistance of A Michowicz and K Rasmussen. This research was presented in part at the 41st Union World Conference on Lung Health, Berlin. Finally, the authors thank all of the men and women who participated in this study.; The study was funded by the Howard Hughes Medical Institute, KwaZulu-Natal Research Initiative for Tuberculosis and HIV. This research was supported by the Harvard Global Health Institute for Global Health, Cambridge, MA, USA (PKD), and the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University, Nashville, TN, USA, R24 TW007988 (PKD). Axis-Shield, Dundee, Scotland, donated the rapid CRP instrument and testing kits. NR 35 TC 11 Z9 11 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 EI 1815-7920 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JAN PY 2014 VL 18 IS 1 BP 20 EP 26 DI 10.5588/ijtld.13.0519 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 286QE UT WOS:000329483000006 PM 24505819 ER PT J AU Field, AE Sonneville, KR Crosby, RD Swanson, SA Eddy, KT Camargo, CA Horton, NJ Micali, N AF Field, Alison E. Sonneville, Kendrin R. Crosby, Ross D. Swanson, Sonja A. Eddy, Kamryn T. Camargo, Carlos A., Jr. Horton, Nicholas J. Micali, Nadia TI Prospective Associations of Concerns About Physique and the Development of Obesity, Binge Drinking, and Drug Use Among Adolescent Boys and Young Adult Men SO JAMA PEDIATRICS LA English DT Article ID COMORBIDITY-SURVEY-REPLICATION; EATING-DISORDERS; GIRLS; PREADOLESCENT; PREVALENCE; BEHAVIORS; OUTCOMES; PEER AB IMPORTANCE Relatively little is known about the prevalence of concerns with physique and eating disorders among males and their relation to subsequent adverse outcomes. A broader range of eating disorders needs to be defined to diagnose these illnesses appropriately in males. OBJECTIVE To investigate whether males with psychiatric symptoms related to disordered eating and concern about physique are more likely to become obese, to start using drugs, to consume alcohol frequently (binge drinking), or to develop high levels of depressive symptoms. DESIGN, SETTING, AND PARTICIPANTS The data come from questionnaires sent every 12 to 36 months from 1999 through 2010 to youth in a prospective cohort study, the Growing Up Today Study. The analysis included 5527 males aged 12 to 18 years in 1999 from across the United States who responded to the Growing Up Today Study questionnaires. MAIN OUTCOMES AND MEASURES Development of obesity and high levels of depressive symptoms and initiation of drug use and binge drinking at least monthly. RESULTS From 1999 through 2011 in at least 1 study year, 9.2% of respondents reported high concerns with muscularity but no bulimic behaviors; 2.4%, high concerns with muscularity and use of supplements, growth hormone derivatives, or anabolic steroids to achieve their desired physique; 2.5%, high concerns with thinness but no bulimic behaviors; and 6.3%, high concerns with thinness and muscularity. For eating disorders, 0.8% had partial-or full-criteria bulimia nervosa or purging disorder and 2.9% had partial or full-criteria binge eating disorder but no association with the outcomes of interest. Infrequent binge eating or purging or overeating without a loss of control were reported by 31.0%. However, independent of age and body mass index, males with high concerns about thinness but not muscularity were more likely to develop high depressive symptoms (odds ratio, 2.72; 95% CI, 1.36-5.44). Males with high concerns about muscularity and thinness were more likely than their peers to use drugs (odds ratio, 2.13; 95% CI, 1.31-3.46), and males with high concerns about muscularity who used supplements and other products to enhance physique were more likely to start binge drinking frequently (2.06; 1.58-2.69) and using drugs (2.16; 1.49-3.11). CONCLUSIONS AND RELEVANCE High concerns with muscularity are relatively common among adolescent boys and young men. Males with these concerns who use potentially unhealthy products to improve their physique are at increased risk of adverse outcomes but may not be recognized by their health care providers as having a weight-related disorder because of the sex-specific presentation. C1 [Field, Alison E.; Sonneville, Kendrin R.] Boston Childrens Hosp, Dept Med, Div Adolescent Young Adult Med, Boston, MA 02115 USA. [Field, Alison E.; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Field, Alison E.; Swanson, Sonja A.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Field, Alison E.; Sonneville, Kendrin R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Field, Alison E.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Crosby, Ross D.] Univ N Dakota, Sch Med & Hlth Sci, Neuropsychiat Res Inst, Fargo, ND USA. [Crosby, Ross D.] Univ N Dakota, Sch Med & Hlth Sci, Dept Clin Neurosci, Fargo, ND USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Eddy, Kamryn T.] Harvard Univ, Sch Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Horton, Nicholas J.] Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. [Micali, Nadia] UCL, Inst Child Hlth, Behav & Brain Sci Unit, London, England. RP Field, AE (reprint author), Boston Childrens Hosp, Dept Med, Div Adolescent Young Adult Med, 300 Longwood Ave,AU Box 17, Boston, MA 02115 USA. EM alison.field@childrens.harvard.edu RI Micali, nadia/E-6829-2010; OI Micali, nadia/0000-0001-5571-2273; Horton, Nicholas/0000-0003-3332-4311; Crosby, Ross/0000-0001-9131-1629 FU National Institutes of Health (NIH) [MH087786, DK59570, DK46200, HL68041, HD049889] FX Data collection for this study was supported by research grants MH087786, DK59570, DK46200, HL68041, and HD049889 from the National Institutes of Health (NIH). NR 20 TC 28 Z9 28 U1 7 U2 42 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JAN PY 2014 VL 168 IS 1 BP 34 EP 39 DI 10.1001/jamapediatrics.2013.2915 PG 6 WC Pediatrics SC Pediatrics GA 291RK UT WOS:000329846600010 PM 24190655 ER PT J AU Feskanich, D Bischoff-Ferrari, HA Frazier, AL Willett, WC AF Feskanich, Diane Bischoff-Ferrari, Heike A. Frazier, A. Lindsay Willett, Walter C. TI Milk Consumption During Teenage Years and Risk of Hip Fractures in Older Adults SO JAMA PEDIATRICS LA English DT Article ID PEAK BONE MASS; HORMONE REPLACEMENT THERAPY; NATIONAL DEATH INDEX; CALCIUM INTAKE; MINERAL DENSITY; ADOLESCENT DIET; FOLLOW-UP; VITAMIN-D; OSTEOPOROTIC FRACTURES; PROSPECTIVE COHORT AB IMPORTANCE Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life. However, its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height. OBJECTIVES To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study over 22 years of follow-up in more than 96 000 white postmenopausal women from the Nurses' Health Study and men aged 50 years and older from the Health Professionals Follow-up Study in the United States. EXPOSURES Frequency of consumption of milk and other foods during ages 13 to 18 years and attained height were reported at baseline. Current diet, weight, smoking, physical activity, medication use, and other risk factors for hip fractures were reported on biennial questionnaires. MAIN OUTCOMES AND MEASURES Cox proportional hazards models were used to calculate relative risks (RRs) of first incidence of hip fracture from low-trauma events per glass (8 fl oz or 240 mL) of milk consumed per day during teenage years. RESULTS During follow-up, 1226 hip fractures were identified in women and 490 in men. After controlling for known risk factors and current milk consumption, each additional glass of milk per day during teenage years was associated with a significant 9% higher risk of hip fracture in men (RR = 1.09; 95% CI, 1.01-1.17). The association was attenuated when height was added to the model (RR = 1.06; 95% CI, 0.98-1.14). Teenage milk consumption was not associated with hip fractures in women (RR = 1.00 per glass per day; 95% CI, 0.95-1.05). CONCLUSIONS AND RELEVANCE Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults. The positive association observed in men was partially mediated through attained height. C1 [Feskanich, Diane; Frazier, A. Lindsay; Willett, Walter C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Feskanich, Diane; Frazier, A. Lindsay; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bischoff-Ferrari, Heike A.] Univ Zurich, Ctr Aging & Mobil, Zurich, Switzerland. [Bischoff-Ferrari, Heike A.] Univ Zurich Hosp, Dept Rheumatol, CH-8091 Zurich, Switzerland. [Bischoff-Ferrari, Heike A.] Univ Zurich Hosp, Inst Phys Med & Rehabil, CH-8091 Zurich, Switzerland. [Frazier, A. Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Feskanich, D (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM diane.feskanich@channing.harvard.edu FU National Institute on Aging [5R03AG030521]; National Cancer Institute [P01CA87969, P01CA055075] FX This research was supported by grant 5R03AG030521 from the National Institute on Aging and grants P01CA87969 and P01CA055075 from the National Cancer Institute. NR 66 TC 11 Z9 12 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JAN PY 2014 VL 168 IS 1 BP 54 EP 60 DI 10.1001/jamapediatrics.2013.3821 PG 7 WC Pediatrics SC Pediatrics GA 291RK UT WOS:000329846600013 PM 24247817 ER PT J AU Pizzirusso, M Lin, J Head, C Marcus, SM Ahmed, S Brau, N Weiss, JJ AF Pizzirusso, Maria Lin, Jenny Head, Cory Marcus, Sue M. Ahmed, Samia Braeu, Norbert Weiss, Jeffrey J. TI Impact of Hepatitis C Treatment Initiation on Adherence to Concomitant Medications SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE adherence; concomitant medications; HCV; HIV; treatment initiation ID SELF-REPORTED ADHERENCE; CHRONIC HCV INFECTION; GENOTYPE 1 INFECTION; VISUAL ANALOG SCALE; ANTIRETROVIRAL ADHERENCE; PEGYLATED INTERFERON; HIV PATIENTS; THERAPY; BOCEPREVIR; TELAPREVIR AB Our study investigated whether initiating hepatitis C virus (HCV) treatment affected adherence to concomitant medications. Mixed-effects linear regression was used to analyze data from 57 patients (29 co-infected with HIV) in a prospective study of HCV treatment-naive patients initiating HCV treatment. Adherence was assessed using structured selfreport at the time of treatment initiation, and at 12 weeks and 24 weeks into treatment. There was no change in adherence to concomitant medications over the first 24 weeks of HCV treatment. There was a significant interaction effect such that the change in adherence to concomitant medications between baseline and 12 weeks differed between the HIV-infected and HIV-uninfected patients. Adherence to concomitant medications in the HIV-infected patients was found to decrease, whereas adherence in the HIV-uninfected patients was found to increase. HIVinfected patients may be more at risk for adherence problems in the first 12 weeks of HCV treatment as compared to HIV-uninfected patients. Copyright (C) 2014 Association of Nurses in AIDS Care C1 [Pizzirusso, Maria; Lin, Jenny; Braeu, Norbert; Weiss, Jeffrey J.] Icahn Sch Med Mt Sinai, New York, NY USA. [Head, Cory] New York City Childrens Ctr, Bronx, NY USA. [Marcus, Sue M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Marcus, Sue M.] Columbia Coll Phys & Surg, New York, NY USA. [Ahmed, Samia; Braeu, Norbert] Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Pizzirusso, M (reprint author), Icahn Sch Med Mt Sinai, New York, NY USA. FU National Institute of Mental Health of the National Institutes of Health [MH071177] FX This study was funded by the National Institute of Mental Health of the National Institutes of Health, grant number MH071177. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. NR 30 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 EI 1552-6917 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD JAN-FEB PY 2014 VL 25 IS 1 BP 23 EP 31 DI 10.1016/j.jana.2013.07.004 PG 9 WC Nursing SC Nursing GA 287FG UT WOS:000329526500005 PM 24070644 ER PT J AU Basile, JN Bloch, MJ AF Basile, Jan N. Bloch, Michael J. TI Analysis of Recent Papers in Hypertension Treatment of Hypertension in the Setting of Acute Intracerebral Hemorrhage: Still No Clear Answer on the Best BP Level to Intervene or What BP Goal to Achieve SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Basile, Jan N.] Med Univ S Carolina, Div Gen Internal Med Geriatr, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. [Bloch, Michael J.] Renown Reg Med Ctr, Renown Inst Heart & Vasc Hlth, Reno, NV USA. RP Bloch, MJ (reprint author), Univ Hlth Syst, 1500 East Second St,Suite 302, Reno, NV 89502 USA. EM michael@bluesprucemed.com NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JAN PY 2014 VL 16 IS 1 BP 1 EP 3 DI 10.1111/jch.12233 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 286SA UT WOS:000329487800006 PM 24325638 ER PT J AU Kostis, JB Sedjro, JE Cabrera, J Cosgrove, NM Pantazopoulos, JS Kostis, WJ Pressel, SL Davis, BR AF Kostis, John B. Sedjro, Jeanine E. Cabrera, Javier Cosgrove, Nora M. Pantazopoulos, John S. Kostis, William J. Pressel, Sara L. Davis, Barry R. TI Visit-to-Visit Blood Pressure Variability and Cardiovascular Death in the Systolic Hypertension in the Elderly Program SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID ANTIHYPERTENSIVE DRUG-TREATMENT; TRANSIENT ISCHEMIC ATTACK; RANDOMIZED-TRIALS; LOWERING REGIMENS; VASCULAR FUNCTION; OLDER PERSONS; RISK-FACTOR; TASK-FORCE; STROKE; ASSOCIATION AB Most studies of an association of visit-to-visit variability of blood pressure with increased risk of future adverse cardiovascular events are of short duration and rarely include a placebo group. Using data from the double-blind, placebo-controlled Systolic Hypertension in the Elderly Program, the authors examined mortality from cardiovascular causes up to 17 years of follow-up using the National Death Index. Visit-to-visit blood pressure variability was associated with cardiovascular death after adjustment for sex, age, serum creatinine, diabetes, body mass index, smoking status, left ventricular failure, and high-density lipoprotein cholesterol. The relationship was significantly stronger in the active treatment group compared with the placebo group. Although this could be the result of an effect of the medications used unrelated to visit-to-visit variability, the data are compatible with the hypothesis that inconsistent adherence leading to missing active medication doses may be an additional explanation for the relationship of visit-to-visit variability with cardiovascular death. C1 [Kostis, John B.; Sedjro, Jeanine E.; Cabrera, Javier; Cosgrove, Nora M.; Pantazopoulos, John S.] Rutgers Robert Wood Johnson Med Sch, Cardiovasc Inst, New Brunswick, NJ 08901 USA. [Cabrera, Javier] Rutgers State Univ, Dept Stat, Piscataway, NJ USA. [Kostis, William J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Pressel, Sara L.; Davis, Barry R.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. RP Kostis, JB (reprint author), Rutgers Robert Wood Johnson Med Sch, Cardiovasc Inst, 125 Paterson St,CAB 5200, New Brunswick, NJ 08901 USA. EM kostis@rwjms.rutgers.edu FU National Heart, Lung, and Blood Institute (NHLBI); National Institute on Aging (NIA); Robert Wood Johnson Foundation (RWJ) FX This work was supported in part by a grant from the National Heart, Lung, and Blood Institute (NHLBI); the National Institute on Aging (NIA); and the Robert Wood Johnson Foundation (RWJ). NR 37 TC 13 Z9 13 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JAN PY 2014 VL 16 IS 1 BP 34 EP 40 DI 10.1111/jch.12230 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 286SA UT WOS:000329487800017 PM 24325609 ER PT J AU Gujral, UP Narayan, KMV Kahn, SE Kanaya, AM AF Gujral, Unjali P. Narayan, K. M. Venkat Kahn, Steven E. Kanaya, Alka M. TI The relative associations of beta-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: The MASALA study SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Type 2 diabetes mellitus; Asian Indians; Insulin sensitivity; beta-cell dysfunction; Ethnicity; Incidence; Impaired glucose tolerance; Impaired fasting glucose ID POPULATION-BASED INCIDENCE; SOUTH ASIANS; RESISTANCE; DYSFUNCTION; PREVALENCE; GLUCOSE; ATHEROSCLEROSIS; MODEL; RISK; US AB Aims: We assessed the relative associations of beta-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States. Methods: A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISIM) estimated insulin sensitivity, and the Disposition Index (DIo) estimated beta-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia. Results: Mean age was 57 +/- 8 years and BMI 26.1 +/- 4.6 kg/m(2). Log ISIM and log DIo were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DIo remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-years) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-beta (OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression. Conclusions: The association of DIo with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-beta with incident glycemic progression implies innate beta-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia. (C) 2014 Elsevier Inc. All rights reserved. C1 [Gujral, Unjali P.; Narayan, K. M. Venkat] Emory Univ, Laney Grad Sch, Grad Div Biomed & Biol Sci, Nutr & Hlth Sci Program, Atlanta, GA 30329 USA. [Narayan, K. M. Venkat] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30329 USA. [Narayan, K. M. Venkat] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30329 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Kanaya, Alka M.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94115 USA. RP Kanaya, AM (reprint author), Univ Calif San Francisco, Box 0320,1545 Divisadero St,Suite 311, San Francisco, CA 94115 USA. EM alka.kanaya@ucsf.edu RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 FU NIH [K23 HL080026-01]; American Heart Association [0855069F]; NIH/NCRR UCSF-CTSI [UL1 RR024131]; Fulbright Nehru Scholars Program; United States Department of Veterans Affairs FX The MASALA study were supported by the NIH [grant no. K23 HL080026-01] and the American Heart Association (Western States Affiliate award #0855069F). This project was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131.UP Gujral was funded by the Fulbright Nehru Scholars Program. SE Kahn was supported by the United States Department of Veterans Affairs. NR 28 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2014 VL 28 IS 1 BP 45 EP 50 DI 10.1016/j.jdiacomp.2013.10.002 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 288DL UT WOS:000329592100011 PM 24211090 ER PT J AU Ismail-Beigi, F Lombardero, MS Escobedo, J Genuth, S Green, J Massaro, E Mooradian, AD Ovalle, F Whitehouse, F Zonszein, J AF Ismail-Beigi, Faramarz Lombardero, Manuel S. Escobedo, Jorge Genuth, Saul Green, Jennifer Massaro, Elaine Mooradian, Arshag D. Ovalle, Fernando Whitehouse, Fred Zonszein, Joel CA Bari 2D Study Grp TI Determinants of successful glycemic control among participants in the BARI 2D Trial: A Post-hoc Analysis SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Cardiovascular disease; Plasma insulin levels; Predictors of glycemic control ID BETA-CELL FUNCTION; TYPE-2 DIABETES-MELLITUS; INSULIN-SECRETION; GLUCOSE; AGE; SENSITIVITY; AMERICANS; METFORMIN; THERAPY; DESIGN AB Objective: The BARI 2D trial compared insulin provision (IP) versus insulin sensitization (IS) for the primary outcome of total mortality in participants with T2DM and cardiovascular disease (CVD). In this analysis we examine baseline characteristics that are associated with successful long-term glycemic control. Research design and methods: In a 2 x 2 factorial design, 2368 participants were randomized to either IP or IS therapy, and to either prompt revascularization with medical therapy or medical therapy alone. Successful long-term glycemic control (success) was defined by simultaneously meeting 1) a mean HbA1c level of <7.0% after each participant's third year of follow-up period, and 2) adherence with medications only from the assigned glycemic treatment arm during >80% of the BARI 2D follow-up. The association between baseline variables and success was determined using unadjusted and adjusted logistic regression models. Results: 1917 participants (962 IP and 955 IS participants) had sufficiently long follow-up and data for this analysis. Among these IP and IS participants, 235 and 335 participants met both criteria of success, respectively (p<0.001). Those not on insulin at entry had higher odds of success (OR 2.25; CI 1.79-2.82) when treated with IS versus IP medications, irrespective of baseline HbA1c levels. Younger age, shorter duration of T2DM, and lower HbA1c at baseline were also each independently associated with higher success when treated with IS versus IP medications. Conclusion: Patients similar to those in the BARI 20 trial may have a higher chance of achieving success with IS versus IP medications if they are younger, have shorter duration of T2DM, have lower HbA1c levels, have moderate or strenuous physically activity, and are not on insulin. In contrast, increasing age, longer duration of T2DM, higher HbA1c, and insulin therapy are associated with increased chance of success if treated with IP medications. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ismail-Beigi, Faramarz; Genuth, Saul] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Ismail-Beigi, Faramarz] Cleveland VA Med Ctr, Cleveland, OH USA. [Lombardero, Manuel S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Escobedo, Jorge] Reg Hosp 1, Clin Res Ctr, Mexican Inst Social Secur, Benito Juarez 03100, DF, Mexico. [Green, Jennifer] Duke Univ, Med Ctr, Dept Med, Div Endocrinol, Durham, NC 27710 USA. [Green, Jennifer] Durham VA Med Ctr, Durham, NC 27710 USA. [Massaro, Elaine] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Mooradian, Arshag D.] Univ Florida, Coll Med, Jacksonville, FL USA. [Ovalle, Fernando] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Ovalle, Fernando] Birmingham VA Med Ctr, Birmingham, AL USA. [Whitehouse, Fred] Henry Ford Hlth Syst, Diabet & Bone & Mineral Dis, Div Endocrinol, Detroit, MI USA. [Zonszein, Joel] Albert Einstein Coll Med, Montefiore Clin Diabet Ctr, Bronx, NY 10467 USA. RP Ismail-Beigi, F (reprint author), Case Western Reserve Univ, Dept Med, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM fxi2@case.edu FU National Heart, Lung and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases [U01 HL061744, U01 HL061746, U01 HL061748, U01 HL063804]; GlaxoSmithKline; Lantheus Medical Imaging, Inc.; Astellas Pharma US, Inc.; Merck Co., Inc.; Abbott Laboratories, Inc.; Pfizer, Inc. FX The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 20) is funded by the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (U01 HL061744, U01 HL061746, U01 HL061748, U01 HL063804).; BARI 2D receives significant supplemental funding from GlaxoSmithKline, and additional funding from Lantheus Medical Imaging, Inc. (formerly Bristol-Myers Squibb Medical Imaging, Inc.), Astellas Pharma US, Inc., Merck & Co., Inc., Abbott Laboratories, Inc. and Pfizer, Inc. Medications and supplies were donated by Abbott Laboratories Ltd., MediSense Products, Bayer Diagnostics, Becton, Dickinson and Company, J. R. Carlson Labs, Centocor, Inc., Eli Lilly and Company, LipoScience, Inc., Merck Sante, Novartis Pharmaceuticals Corporation, and Novo Nordisk, Inc. NR 32 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2014 VL 28 IS 1 BP 101 EP 109 DI 10.1016/j.jdiacomp.2013.01.006 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 288DL UT WOS:000329592100021 PM 23478173 ER PT J AU Hoffman, RM McNaughton-Collins, M AF Hoffman, Richard M. McNaughton-Collins, Mary TI The Superiority of Patient Engagement and Shared Decision-Making in Noninferiority Trials SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Hoffman, Richard M.] New Mexico VA Hlth Care Syst, Med Serv, Albuquerque, NM 87108 USA. [McNaughton-Collins, Mary] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Hoffman, RM (reprint author), New Mexico VA Hlth Care Syst, Med Serv, 1501 San Pedro Dr SE, Albuquerque, NM 87108 USA. EM rhoffman@unm.edu NR 6 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 16 EP 17 DI 10.1007/s11606-013-2593-z PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900007 PM 23979687 ER PT J AU Linzer, M Levine, R Meltzer, D Poplau, S Warde, C West, CP AF Linzer, Mark Levine, Rachel Meltzer, David Poplau, Sara Warde, Carole West, Colin P. TI 10 Bold Steps to Prevent Burnout in General Internal Medicine SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Linzer, Mark; Poplau, Sara] Hennepin Cty Med Ctr, Div Gen Internal Med, Minneapolis, MN 55415 USA. [Linzer, Mark] Univ Minnesota, Minneapolis, MN USA. [Levine, Rachel] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Meltzer, David] Univ Chicago, Chicago, IL 60637 USA. [Warde, Carole] Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA. [Warde, Carole] Univ Calif Los Angeles, Los Angeles, CA USA. [West, Colin P.] Mayo Clin, Rochester, MN USA. RP Linzer, M (reprint author), Hennepin Cty Med Ctr, Div Internal Med, 701 Pk Ave, Minneapolis, MN 55415 USA. EM Mark.linzer@hcmed.org FU AHRQ HHS [R18 HS018160]; NIA NIH HHS [K24 AG031326] NR 5 TC 30 Z9 30 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 18 EP 20 DI 10.1007/s11606-013-2597-8 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900008 PM 24002633 ER PT J AU Westergaard, RP Beach, MC Saha, S Jacobs, EA AF Westergaard, Ryan P. Beach, Mary Catherine Saha, Somnath Jacobs, Elizabeth A. TI Racial/Ethnic Differences in Trust in Health Care: HIV Conspiracy Beliefs and Vaccine Research Participation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE trust in health care; HIV vaccine research; conspiracy beliefs ID AFRICAN-AMERICANS; CLINICAL-TRIALS; MALE CIRCUMCISION; INFECTED PATIENTS; UNITED-STATES; FOLLOW-UP; DISPARITIES; PREVENTION; MEN; HIV/AIDS AB Prior research has documented a high prevalence of conspiracy beliefs about the origin of the human immunodeficiency virus (HIV) and the role of the government in the acquired immunodeficiency syndrome (AIDS) epidemic, particularly among racial and ethnic minorities in the United States. Whether such beliefs are a barrier to participation in HIV prevention research is not known. To understand the prevalence of HIV conspiracy beliefs and their relationship to willingness to participate in HIV vaccine research among three racial/ethnic groups. Cross-sectional survey. Six hundred and one community-recruited volunteers (33.0 % White, 32.5 % Mexican American, and 34.5 % African American). We evaluated the level of agreement with six previously described HIV conspiracy beliefs, trust in medical research, and willingness to participate in HIV vaccine research. Multivariate models were used to compare these parameters among the three racial/ethnic groups while controlling for the potential confounding effects of socioeconomic status, access to health care, and other demographic factors. African Americans, Mexican Americans, and whites had similar levels of distrust in medical research. African and Mexican Americans were more likely to endorse one or more of six HIV conspiracy beliefs than whites (59.0 % and 58.6 % versus 38.9 %, respectively, P < 0.001), but were significantly more willing to participate in HIV vaccine research (ORs 1.58, CI 1.10-2.25 and 2.53, CI 1.75-3.66, respectively). Among respondents of all racial/ethnic groups, endorsing HIV conspiracy beliefs was not associated with willingness to participate in research. HIV conspiracy beliefs, while common among all racial and ethnic groups in the United States, do not preclude willingness to participate in HIV prevention research. C1 [Westergaard, Ryan P.; Jacobs, Elizabeth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53715 USA. [Westergaard, Ryan P.; Jacobs, Elizabeth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Beach, Mary Catherine] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Jacobs, Elizabeth A.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Madison, WI USA. RP Westergaard, RP (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, MFCB 5220, Madison, WI 53715 USA. EM rpw@medicine.wisc.edu FU National Institutes of Health [1R21HD057473-01A1]; NIH [K23DA032306]; Department of Medicine; Wisconsin Partnership Program [NCATS9_U54_TR000021]; Health Innovation Program at the University of Wisconsin School of Medicine and Public Health; Department of Veterans Affairs FX This research was funded by the National Institutes of Health (1R21HD057473-01A1). Dr. Westergaard received support from NIH grant K23DA032306. Dr. Jacobs has received additional support from the Department of Medicine, the Wisconsin Partnership Program (NCATS9_U54_TR000021), and the Health Innovation Program at the University of Wisconsin School of Medicine and Public Health. Dr. Saha was supported by the Department of Veterans Affairs. The opinions expressed in this paper are those of the authors and not necessarily those of the U.S. Department of Veterans Affairs. NR 46 TC 7 Z9 7 U1 4 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 140 EP 146 DI 10.1007/s11606-013-2554-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900028 PM 23979684 ER PT J AU Oslin, DW Lynch, KG Maisto, SA Lantinga, LJ McKay, JR Possemato, K Ingram, E Wierzbicki, M AF Oslin, David W. Lynch, Kevin G. Maisto, Stephen A. Lantinga, Larry J. McKay, James R. Possemato, Kyle Ingram, Erin Wierzbicki, Michael TI A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE addiction; primary care; treatment; randomized clinical trial ID BRIEF INTERVENTIONS; USE DISORDERS; DEPENDENCE; NALTREXONE; METAANALYSIS; POPULATIONS; RELIABILITY; ACAMPROSATE; EFFICACY; MISUSE AB Alcohol use disorder is one of the leading causes of disability worldwide. Despite the availability of efficacious treatments, few individuals with an alcohol use disorder are actively engaged in treatment. Available evidence suggests that primary care may play a crucial role in the identification of patients with an alcohol use disorder, delivery of interventions, and the success of treatment. The principal aims of this study were to test the effectiveness of a primary care-based Alcohol Care Management (ACM) program for alcohol use disorder and treatment engagement in veterans. The design of the study was a 26-week single-blind randomized clinical trial. The study was conducted in the primary care practices at three VA medical centers. Participants were randomly assigned to treatment in ACM or standard treatment in a specialty outpatient addiction treatment program. One hundred and sixty-three alcohol-dependent veterans were randomized. ACM focused on the use of pharmacotherapy and psychosocial support. ACM was delivered in-person or by telephone within the primary care clinic. Engagement in treatment and heavy alcohol consumption. The ACM condition had a significantly higher proportion of participants engaged in treatment over the 26 weeks [OR = 5.36, 95 % CI = (2.99, 9.59)]. The percentage of heavy drinking days were significantly lower in the ACM condition [OR = 2.16, 95 % CI = (1.27, 3.66)], while overall abstinence did not differ between groups. Results demonstrate that treatment for an alcohol use disorder can be delivered effectively within primary care, leading to greater rates of engagement in treatment and greater reductions in heavy drinking. C1 [Oslin, David W.; McKay, James R.; Ingram, Erin] Univ Penn, Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Oslin, David W.; Lynch, Kevin G.; McKay, James R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Maisto, Stephen A.; Lantinga, Larry J.; Possemato, Kyle] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Maisto, Stephen A.; Lantinga, Larry J.; Possemato, Kyle] VISN2, Dept Vet Affairs, Ctr Integrated Healthcare, Syracuse, NY USA. [Wierzbicki, Michael] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Oslin, DW (reprint author), Univ Penn, Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. EM oslin@upenn.edu FU Health Services Research and Development Program of the Department of Veteran Affairs (IIR); VISN 4 Mental Illness Research, Education, and Clinical Center at the Philadelphia VA Medical Center; VISN 2 Center for Integrated Healthcare; Career Development Award [K05 AA16928]; NIDA [K24 DA029062]; NIAAA [P01-AA016821] FX Supported, for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript, by the following sources:; Health Services Research and Development Program of the Department of Veteran Affairs (IIR); The VISN 4 Mental Illness Research, Education, and Clinical Center at the Philadelphia VA Medical Center; The VISN 2 Center for Integrated Healthcare; Career Development Award [K05 AA16928 (Dr. Maisto)]; NIDA (K24 DA029062) and NIAAA (P01-AA016821) (Dr. McKay) NR 33 TC 23 Z9 23 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 162 EP 168 DI 10.1007/s11606-013-2625-8 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900031 PM 24052453 ER PT J AU Malte, CA AF Malte, Carol A. TI Capsule Commentary on Oslin et al., A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID BRIEF INTERVENTION; DEPENDENCE C1 VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. RP Malte, CA (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. EM Carol.malte@va.gov NR 5 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 184 EP 184 DI 10.1007/s11606-013-2656-1 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900041 PM 24129861 ER PT J AU Ranard, BL Ha, YP Meisel, ZF Asch, DA Hill, SS Becker, LB Seymour, AK Merchant, RM AF Ranard, Benjamin L. Ha, Yoonhee P. Meisel, Zachary F. Asch, David A. Hill, Shawndra S. Becker, Lance B. Seymour, Anne K. Merchant, Raina M. TI Crowdsourcing-Harnessing the Masses to Advance Health and Medicine, a Systematic Review SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE crowdsourcing; crowd sourcing; citizen scientist; citizen science; human computing ID DISTRIBUTED HUMAN INTELLIGENCE; FOLDING GAME PLAYERS; CT COLONOGRAPHY; ONLINE GAME AB Crowdsourcing research allows investigators to engage thousands of people to provide either data or data analysis. However, prior work has not documented the use of crowdsourcing in health and medical research. We sought to systematically review the literature to describe the scope of crowdsourcing in health research and to create a taxonomy to characterize past uses of this methodology for health and medical research. PubMed, Embase, and CINAHL through March 2013. Primary peer-reviewed literature that used crowdsourcing for health research. Two authors independently screened studies and abstracted data, including demographics of the crowd engaged and approaches to crowdsourcing. Twenty-one health-related studies utilizing crowdsourcing met eligibility criteria. Four distinct types of crowdsourcing tasks were identified: problem solving, data processing, surveillance/monitoring, and surveying. These studies collectively engaged a crowd of > 136,395 people, yet few studies reported demographics of the crowd. Only one (5 %) reported age, sex, and race statistics, and seven (33 %) reported at least one of these descriptors. Most reports included data on crowdsourcing logistics such as the length of crowdsourcing (n = 18, 86 %) and time to complete crowdsourcing task (n = 15, 71 %). All articles (n = 21, 100 %) reported employing some method for validating or improving the quality of data reported from the crowd. Gray literature not searched and only a sample of online survey articles included. Utilizing crowdsourcing can improve the quality, cost, and speed of a research project while engaging large segments of the public and creating novel science. Standardized guidelines are needed on crowdsourcing metrics that should be collected and reported to provide clarity and comparability in methods. C1 [Ranard, Benjamin L.; Ha, Yoonhee P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.; Merchant, Raina M.] Univ Penn, Penn Med Ctr Innovat, Philadelphia, PA 19104 USA. [Meisel, Zachary F.; Asch, David A.; Merchant, Raina M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Meisel, Zachary F.; Becker, Lance B.; Merchant, Raina M.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Asch, David A.; Hill, Shawndra S.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Seymour, Anne K.] Univ Penn, Univ Penn Lib, Philadelphia, PA 19104 USA. RP Merchant, RM (reprint author), Univ Penn, Perelman Sch Med, 423 Guardian Dr,Blockley Hall, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Seymour, Anne/0000-0002-4285-7702; Asch, David/0000-0002-7970-286X FU NIH, K23 grant [10714038] FX NIH, K23 grant 10714038 (Merchant). NR 37 TC 56 Z9 56 U1 6 U2 57 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 187 EP 203 DI 10.1007/s11606-013-2536-8 PG 17 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900044 PM 23843021 ER PT J AU Ly, DP Glied, SA AF Ly, Dan P. Glied, Sherry A. TI The Impact of Managed Care Contracting on Physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE managed care contracts; administrative costs; time with patients; physician income ID COSTS AB Prior literature suggests that the fragmented U.S. health care system places a large administrative burden on physicians. Less is known about how this burden varies with physician contracting practices. To assess the extent to which physician practice outcomes vary with the number of managed care contracts held or the availability of such contracts. We perform secondary data analyses of the first four rounds of the nationally representative Community Tracking Study Physician Survey (1996-2005), which includes 36,340 physicians (21,567 PCPs [primary care physicians] and 14,773 specialists) across the four survey periods. Our measures include reported hours in patient care, share of hours outside patient care, adequacy of time with patients, career satisfaction, and income. Doctors who contract with more plans report spending more time in patient care (per 11 additional contracts, about 30 min per week for PCPs and 20 min per week for specialists), report spending a modestly larger share of their time outside patient care (per 11 additional contracts, about 10 min per week for PCPs and specialists), are slightly more likely to report inadequate time with patients (odds ratio 1.005 per additional contract for PCPs), and earn higher incomes (per 11 additional contracts, about 3 % more per year for specialists). Contracting opportunities confer significant benefits on physicians, although they do add modest costs in terms of time spent outside patient care and lower adequacy of time with patients. Simplifications that reduce the administrative burden of contracting may improve care by optimizing allocation of physician effort. C1 [Ly, Dan P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Glied, Sherry A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Hlth Policy & Management, New York, NY USA. RP Ly, DP (reprint author), Massachusetts Gen Hosp, Dept Med, 10 Emerson Pl,Rm 10G, Boston, MA 02114 USA. EM dply@partners.org NR 13 TC 2 Z9 2 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 237 EP 242 DI 10.1007/s11606-013-2589-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900050 PM 24002628 ER PT J AU Anaya, A Plantmason, L Dhaliwal, G AF Anaya, Andres Plantmason, Lee Dhaliwal, Gurpreet TI Back Attack SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE decision making; clinical problem solving; back pain ID PARASPINAL COMPARTMENT SYNDROME; PAIN; RHABDOMYOLYSIS C1 [Anaya, Andres] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Plantmason, Lee] Univ So Calif, Dept Emergency Med, Los Angeles, CA 90033 USA. [Plantmason, Lee] Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Plantmason, L (reprint author), Univ So Calif, Dept Emergency Med, 2051 Marengo St Inpatient Tower Room C1A100, Los Angeles, CA 90033 USA. EM lplantma@gmail.com NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2014 VL 29 IS 1 BP 255 EP 259 DI 10.1007/s11606-013-2487-0 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 284WR UT WOS:000329352900056 PM 23733373 ER PT J AU Mudgal, CS Klausmeyer, MA AF Mudgal, Chaitanya S. Klausmeyer, Melissa A. TI Hook of Hamate Fractures: Location and Tendon Rupture Reply SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter ID SECONDARY C1 [Mudgal, Chaitanya S.; Klausmeyer, Melissa A.] Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2014 VL 39 IS 1 BP 176 EP 177 DI 10.1016/j.jhsa.2013.11.019 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 288CZ UT WOS:000329590900037 PM 24369952 ER PT J AU Nguyen, R Jett, K Harris, GJ Cai, WL Friedman, JM Mautner, VF AF Nguyen, Rosa Jett, Kimberly Harris, Gordon J. Cai, Wenli Friedman, Jan M. Mautner, Victor-Felix TI Benign whole body tumor volume is a risk factor for malignant peripheral nerve sheath tumors in neurofibromatosis type 1 SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Malignant peripheral nerve sheath tumor; MRI scan; Neurofibromatosis 1; Plexiform neurofibroma; Whole body MRI ID PLEXIFORM NEUROFIBROMAS; NF1; MORTALITY; SURVIVAL; BURDEN; IMAGES; MRI AB The purpose of this study is to determine whether benign whole body tumor volume of plexiform neurofibromas (PNs) is a risk factor for malignant peripheral nerve sheath tumors (MPNST) in individuals with neurofibromatosis type 1 (NF1). Thirty-one NF1 patients with MPNSTs and 62 age- and sex-matched NF1 patients without MPNSTs, who had undergone whole body magnetic resonance imaging (MRI) were analyzed for benign whole body tumor volume. Mann-Whitney U test, Wilcoxon signed ranks test, Fisher's exact test (two-tailed), and logistic regression analysis were used for statistical analysis. Sixteen percent of all patients with MPNST did not have internal PN. The median whole body benign tumor volume in patients with PN was 352.0 mL among the MPNST group and 3.8 mL in the comparison group (p < 0.001). When the patients were stratified by age as younger or older than 30 years (median age of MPNST diagnosis), the median benign whole body tumor volume was 693.0 mL in MPNST patients and 0.0 mL in control patients younger than 30 years (p < 0.001). The mean number of PNs in MPNST patients was 2.8 (range 0-13, median 2.0) and 1.4 (range 0-13, median 1.0) in patients without MPNST (p = 0.001). The risk of MPNST development increased 0.2 % with each additional mL of benign PN volume (adjusted odds ratio [OR] = 1.002, 95 % confidence interval [CI] 1.001-1.003, p = 0.005) and was higher in patients younger than 30 years (adjusted OR = 1.007, 95 % CI 1.002-1.012, p = 0.003). Higher numbers of PNs, larger whole body benign tumor volume, and younger age are important risk factors for MPNST. We identified a subgroup of patients with MPNST without internal PN on MRI and the lack of correlation of MPNST development with tumor burden in older patients. These findings may alter our belief that all MPNSTs arise from pre-existing PNs and suggest that surveillance MRI based on clinical suspicion may be warranted in older patients, respectively. C1 [Nguyen, Rosa] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Jett, Kimberly; Friedman, Jan M.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada. [Harris, Gordon J.; Cai, Wenli] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Mautner, Victor-Felix] Univ Hosp Hamburg Eppendorf, Dept Neurol, D-20246 Hamburg, Germany. RP Nguyen, R (reprint author), Univ Maryland, Dept Pediat, 22 South Greene St,N5W70, Baltimore, MD 21201 USA. EM rosi.nguyen@gmail.com OI Friedman, Jan/0000-0002-7482-9570 FU Deutsche Krebshilfe [106982] FX This work was supported by "Deutsche Krebshilfe", grant number 106982 to VFM. NR 13 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2014 VL 116 IS 2 BP 307 EP 313 DI 10.1007/s11060-013-1293-1 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 288OW UT WOS:000329622300013 PM 24166582 ER PT J AU Mangla, R Ginat, DT Kamalian, S Milano, MT Korones, DN Walter, KA Ekholm, S AF Mangla, Rajiv Ginat, Daniel Thomas Kamalian, Shervin Milano, Michael T. Korones, David N. Walter, Kevin A. Ekholm, Sven TI Correlation between progression free survival and dynamic susceptibility contrast MRI perfusion in WHO grade III glioma subtypes SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE MR perfusion; Grade III astrocytoma; Progression free survival ID CEREBRAL BLOOD-VOLUME; GROWTH-FACTOR VEGF; TUMOR GRADE; GLIOBLASTOMA-MULTIFORME; PROGNOSTIC-FACTORS; MALIGNANT GLIOMA; BRAIN-TUMORS; ENHANCED MR; OLIGODENDROGLIOMAS; ASTROCYTOMAS AB The purpose of this study was to determine whether dynamic susceptibility contrast MR perfusion relative cerebral blood volume (rCBV) correlates with prognosis of World Health Organization (WHO) grade III glial tumors and their different subtypes. Retrospective evaluation of pre-treatment tumor rCBV derived from dynamic susceptibility contrast MR perfusion was performed in 34 patients with histopathologically diagnosed WHO grade III glial tumors (anaplastic astrocytomas (n = 20), oligodendrogliomas (n = 4), and oligoastrocytomas (n = 10)). Progression free survival was correlated with rCBV using Spearman rank analysis. ROC curve analysis was performed to determine the operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time. For all grade III tumors (n = 34) the mean rCBV was 2.51 with a progression free survival of 705.5 days. The mean rCBV of anaplastic astrocytomas was 2.47 with progression free survival 495.2 days. In contrast, the mean rCBV for oligodendroglial tumors was 2.56 with a progression free survival of 1005.6 days. Although there was no significant correlation between rCBV and progression free survival among all types of grade III gliomas (P = 0.12), among anaplastic astrocytomas there was a significant correlation between pretreatment rCBV and progression free survival with correlation coefficient of -0.51 (P = 0.02). The operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time (446.5 days) was 2.86 with 78 % accuracy and there was a significant difference between the survival of patients with anaplastic astrocytomas in the dichotomized groups (P = 0.0009). Pre-treatment rCBV may serve as a prognostic imaging biomarker for anaplastic astrocytomas, but not grade III oligodendroglioma tumors. C1 [Mangla, Rajiv; Ekholm, Sven] Univ Rochester, Sch Med & Dent, Dept Imaging Sci, Rochester, NY USA. [Ginat, Daniel Thomas] Univ Chicago, Med Ctr, Dept Radiol, Chicago, IL 60637 USA. [Kamalian, Shervin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Milano, Michael T.] Univ Rochester, Sch Med & Dent, Dept Radiat Oncol, Rochester, NY USA. [Korones, David N.] Univ Rochester, Sch Med & Dent, Dept Pediat Oncol, Rochester, NY USA. [Walter, Kevin A.] Univ Rochester, Sch Med & Dent, Dept Neurosurg, Rochester, NY USA. RP Ginat, DT (reprint author), Univ Chicago, Med Ctr, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com RI Kamalian, Shervin/D-7667-2013 OI Kamalian, Shervin/0000-0001-8962-4773 NR 31 TC 10 Z9 11 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2014 VL 116 IS 2 BP 325 EP 331 DI 10.1007/s11060-013-1298-9 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 288OW UT WOS:000329622300015 PM 24178441 ER PT J AU Jenkins, PE Hoste, RR Doyle, AC Eddy, K Crosby, RD Hill, L Powers, P Mitchell, JE Le Grange, D AF Jenkins, Paul E. Hoste, Renee Rienecke Doyle, Angela Celio Eddy, Kamryn Crosby, Ross D. Hill, Laura Powers, Pauline Mitchell, James E. Le Grange, Daniel TI Health-related quality of life among adolescents with eating disorders SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Adolescence; Eating disorders; Quality of life; Anorexia nervosa; Bulimia nervosa ID SELF-REPORT QUESTIONNAIRE; BULIMIA-NERVOSA; ANOREXIA-NERVOSA; COMMUNITY SAMPLE; WEIGHT CONTROL; YOUNG-ADULTS; SURVEY SF-36; IMPAIRMENT; WOMEN; OVERWEIGHT AB Objective: Health-related quality of life (HRQoL) is an emerging area of research in eating disorders (EDs) that has not been examined in adolescents in detail. The aim of the current study is to investigate HRQoL in an adolescent ED sample, examining the impact of ED symptoms on HRQoL. Methods: Sixty-seven treatment-seeking adolescents (57 females) with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (EDNOS) completed self-report measures of HRQoL and ED symptoms. Results: Participants reported poorer HRQoL in mental health domains than in physical health domains. Disordered attitudes, binge eating, and compensatory behaviors were associated with poorer mental health HRQoL, and body dissatisfaction was associated with poorer physical health HRQoL. Conclusion: The current study assessed HRQoL among adolescents with EDs, finding several consistencies with the literature on adults with EDs. Future research should compare adolescents and adults with EDs on HRQoL. (C) 2013 Elsevier Inc. All rights reserved. C1 [Jenkins, Paul E.] Univ Birmingham, Birmingham B15 2TT, W Midlands, England. [Hoste, Renee Rienecke] Univ Michigan, Ann Arbor, MI 48109 USA. [Doyle, Angela Celio] Evidence Based Treatment Ctr Seattle, Seattle, WA USA. [Eddy, Kamryn] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Crosby, Ross D.; Mitchell, James E.] Univ N Dakota, Sch Med & Hlth Sci, Neuropsychiat Res Inst, Grand Forks, ND 58201 USA. [Powers, Pauline] Univ S Florida, Tampa, FL 33620 USA. [Le Grange, Daniel] Univ Chicago, Chicago, IL 60637 USA. RP Jenkins, PE (reprint author), Warneford Hosp, Eating Disorders Serv, Cotswold House,Warneford Lane, Oxford OX3 7JX, England. EM pej106@gmail.com OI Crosby, Ross/0000-0001-9131-1629 NR 54 TC 5 Z9 5 U1 4 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JAN PY 2014 VL 76 IS 1 BP 1 EP 5 DI 10.1016/j.jpsychores.2013.11.006 PG 5 WC Psychiatry SC Psychiatry GA 288DI UT WOS:000329591800001 PM 24360133 ER PT J AU Malaisrie, SC Barnhart, GR Farivar, RS Mehall, J Hummel, B Rodriguez, E Anderson, M Lewis, C Hargrove, C Ailawadi, G Goldman, S Khan, J Moront, M Grossi, E Roselli, EE Agnihotri, A Mack, MJ Smith, JM Thourani, VH Duhay, FG Kocis, MT Ryan, WH AF Malaisrie, S. Chris Barnhart, Glenn R. Farivar, R. Saeid Mehall, John Hummel, Brian Rodriguez, Evelio Anderson, Mark Lewis, Clifton Hargrove, Clark Ailawadi, Gorav Goldman, Scott Khan, Junaid Moront, Michael Grossi, Eugene Roselli, Eric E. Agnihotri, Arvind Mack, Michael J. Smith, J. Michael Thourani, Vinod H. Duhay, Francis G. Kocis, Mark T. Ryan, William H. TI Current era minimally invasive aortic valve replacement: Techniques and practice SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Review ID RIGHT ANTERIOR MINITHORACOTOMY; SURGERY; OUTCOMES; OPERATIONS; STERNOTOMY; MINISTERNOTOMY; IMPACT AB Background: Since the first aortic valve replacement through a right thoracotomy was reported in 1993, upper hemisternotomy and right anterior thoracotomy have become the predominant approaches for minimally invasive aortic valve replacement. Clinical studies have documented equivalent operative mortality, less bleeding, and reduced intensive care/hospital stay compared with conventional sternotomy despite longer procedure times. However, comparative trials face challenges due to patient preference, surgeon bias, and the lack of a standardized minimally invasive surgical approach. Methods: Twenty cardiothoracic surgeons from 19 institutions across the United States, with a combined experience of nearly 5000 minimally invasive aortic valve replacement operations, formed a working group to develop a basis for a standardized approach to patient evaluation, operative technique, and postoperative care. In addition, a stepwise learning program for surgeons was outlined. Results: Improved cosmesis, less pain and narcotic use, and faster recovery have been reported and generally accepted by patients and by surgeons performing minimally invasive aortic valve replacement. These benefits are more likely to be verified with standardization of the procedure itself, which will greatly facilitate the design and implementation of future clinical studies. Conclusions: Surgeons interested in learning and performing minimally invasive aortic valve replacement must have expertise in conventional aortic valve replacement at centers with adequate case volumes. A team approach that coordinates efforts of the surgeon, anesthesiologist, perfusionist, and nurses is required to achieve the best clinical outcomes. By first developing fundamental minimally invasive skills using specialized cannulation techniques, neck lines, and long-shafted instruments in the setting of conventional full sternotomy, the safest operative environment is afforded to patients. C1 [Malaisrie, S. Chris] Northwestern Univ, Chicago, IL 60611 USA. [Barnhart, Glenn R.] Swedish Med Ctr, Seattle, WA USA. [Farivar, R. Saeid] Univ Penn, Philadelphia, PA 19104 USA. [Mehall, John] Penrose St Francis Hlth Syst, Colorado Springs, CO USA. [Hummel, Brian] Gulf Coast Cardiothorac, Ft Myers, FL USA. [Rodriguez, Evelio] St Thomas Heart Hosp, Nashville, TN USA. [Anderson, Mark] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Lewis, Clifton] Cardiothorac Surg PC, Birmingham, AL USA. [Hargrove, Clark] Penn Presbyterian Med Ctr, Philadelphia, PA USA. [Ailawadi, Gorav] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Goldman, Scott] Lankenau Hosp, Wynnewood, PA USA. [Khan, Junaid] Alta Bates Summit Med Ctr, Oakland, CA USA. [Moront, Michael] Toledo Hosp, Toledo, OH USA. [Grossi, Eugene] NYU, Sch Med, New York, NY USA. [Roselli, Eric E.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Agnihotri, Arvind] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mack, Michael J.; Ryan, William H.] Baylor Heart Hosp, Dallas, TX 75219 USA. [Smith, J. Michael] Good Samaritan Hosp, Hatton Inst, Cincinnati, OH USA. [Thourani, Vinod H.] Emory Univ, Sch Med, Atlanta, GA USA. [Duhay, Francis G.; Kocis, Mark T.] Edwards Lifesci, Irvine, CA USA. RP Ryan, WH (reprint author), Baylor Heart Hosp, 4646 Kelsey Rd, Dallas, TX 75219 USA. EM whryanmd@yahoo.com OI GROSSI, eugene/0000-0002-2066-7035 NR 23 TC 27 Z9 27 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2014 VL 147 IS 1 BP 6 EP 14 DI 10.1016/j.jtcvs.2013.08.086 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 289ZY UT WOS:000329722600008 PM 24183904 ER PT J AU Korst, RJ Bezjak, A Blackmon, S Choi, N Fidias, P Liu, G Marx, A Wright, C Mock, S Rutledge, JR Keshavjee, S AF Korst, Robert J. Bezjak, Andrea Blackmon, Shanda Choi, Noah Fidias, Panos Liu, Geoffrey Marx, Alexander Wright, Cameron Mock, Susan Rutledge, John R. Keshavjee, Shaf TI Neoadjuvant chemoradiotherapy for locally advanced thymic tumors: A phase II, multi-institutional clinical trial SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID COMPUTED-TOMOGRAPHY; SURGICAL RESECTION; RADIATION-THERAPY; INVASIVE THYMOMA; STAGE-III; CHEMOTHERAPY AB Objective: To determine the response rate, toxicity, and rate of complete resection after induction chemoradiotherapy for locally advanced thymic tumors, which were defined by specific radiographic criteria. Methods: A single-arm, pilot trial was conducted at 4 institutions. Patients with thymoma or thymic carcinoma who met specific criteria on computed tomography were accrued. Induction therapy consisted of 2 cycles of cisplatin and etoposide combined with 45 Gy of thoracic radiotherapy. Patients underwent computed tomography and positron emission tomography before and after induction therapy and then resection was attempted. Postoperative chemoradiotherapy was administered in selected patients. The primary endpoint was the pathologic response to induction therapy. The secondary endpoints were toxicity, surgical complications, radiographic response, and the rate of R0 resection. Results: A total of 22 patients were accrued during a 5-year period (1 patient withdrew before starting induction therapy). Of the 22 patients, 21 completed induction therapy, and 9 (41%) experienced grade 3 or 4 toxicity. A total of 10 patients had a partial radiographic response and 11 had stable disease. Of the 21 patients, 17 (77%) underwent an R0 resection, 3 (14%) an R1 resection, and 1 (5%) underwent debulking. Eight patients sustained surgical complications (36%), and two patients (9%) died postoperatively. Of the 21 patients, 13 (62%) had either thymic carcinoma or B3 thymoma and 15 (71%) had either Masaoka stage III or IV disease. No patient had a complete pathologic response, but 5 specimens (24%) had <10% viable tumor. Conclusions: The present induction chemoradiotherapy protocol, which used specific computed tomography inclusion criteria to successfully select locally advanced thymic tumors, appeared to be tolerable and resulted in a high rate of complete surgical resection. C1 [Korst, Robert J.; Mock, Susan; Rutledge, John R.] Daniel & Gloria Blumenthal Canc Ctr, Paramus, NJ USA. [Korst, Robert J.] Valley Hlth Syst, Valley Hosp, Dept Surg, Div Thorac Surg, Ridgewood, NJ USA. [Korst, Robert J.; Bezjak, Andrea; Liu, Geoffrey; Marx, Alexander; Wright, Cameron; Keshavjee, Shaf] Int Thym Malignancy Interest Grp, Ardsley, NY USA. [Bezjak, Andrea] Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada. [Blackmon, Shanda] Methodist Hosp, Dept Surg, Thorac Surg Sect, Houston, TX 77030 USA. [Choi, Noah] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Fidias, Panos] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Liu, Geoffrey] Princess Margaret Canc Ctr, Dept Med, Toronto, ON, Canada. [Liu, Geoffrey] Princess Margaret Canc Ctr, Dept Med Biophys, Toronto, ON, Canada. [Marx, Alexander] Heidelberg Univ, Univ Med Ctr Mannheim, Inst Pathol, Mannheim, Germany. [Wright, Cameron] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Keshavjee, Shaf] Toronto Gen Hosp, Dept Surg, Div Thorac Surg, Toronto, ON, Canada. RP Korst, RJ (reprint author), Valley Hlth Syst, Valley Hosp, Dept Surg, Div Thorac Surg, 1 Valley Hlth Plaza, Paramus, NJ 07652 USA. EM korsro@valleyhealth.com RI Liu, Geoffrey/N-4421-2016 FU Valley Hospital Foundation FX This study was funded, in part, by the Valley Hospital Foundation. NR 18 TC 33 Z9 35 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2014 VL 147 IS 1 BP 36 EP U755 DI 10.1016/j.jtcvs.2013.08.061 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 289ZY UT WOS:000329722600013 PM 24139613 ER PT J AU Ackman, JB AF Ackman, Jeanne B. TI A Practical Guide to Nonvascular Thoracic Magnetic Resonance Imaging SO JOURNAL OF THORACIC IMAGING LA English DT Review DE thoracic MRI; thoracic MRI protocols; MRI acronyms; MRI trade-offs; motion artifact; cardiac gating; breath-hold imaging; MRI interpretation ID CYSTIC-FIBROSIS; MRI; CHEST; CT; APPEARANCE; DISORDERS; SEQUENCE; DISEASE; LESIONS; MDCT AB There is increasing perception that thoracic magnetic resonance imaging (MRI) is underutilized. Various obstacles to implementation and utilization of thoracic MRI can be overcome with continuous updating, improvement, and standardization of thoracic MRI protocols, close collaboration with MRI technologists, continued education of MRI technologists, radiologists, and referring health care providers, and incorporation of MRI training into thoracic imaging fellowship programs. The purpose of this article is to share the author's experience in developing a successful nonvascular thoracic MRI practice, discuss the fundamentals of nonvascular thoracic MRI, and provide a how-to manual for its performance. C1 [Ackman, Jeanne B.] Harvard Univ, Sch Med, Boston, MA USA. [Ackman, Jeanne B.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. RP Ackman, JB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging & Intervent, Founders House 202,55 Fruit St, Boston, MA 02114 USA. EM jackman@partners.org NR 27 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD JAN PY 2014 VL 29 IS 1 BP 17 EP 29 DI 10.1097/RTI.0000000000000056 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 290HG UT WOS:000329744900006 PM 24361974 ER PT J AU Sidhu, MS Uthamalingam, S Ahmed, W Engel, LC Vorasettakarnkij, Y Lee, AM Hoffmann, U Brady, T Abbara, S Ghoshhajra, BB AF Sidhu, Manavjot S. Uthamalingam, Shanmugam Ahmed, Waleed Engel, Leif-Christopher Vorasettakarnkij, Yongkasem Lee, Ashley M. Hoffmann, Udo Brady, Thomas Abbara, Suhny Ghoshhajra, Brian B. TI Defining Left Ventricular Noncompaction Using Cardiac Computed Tomography SO JOURNAL OF THORACIC IMAGING LA English DT Article DE left ventricular noncompaction; cardiomyopathy; cardiac computed tomography ID NON-COMPACTION; DISTINCT CARDIOMYOPATHY; MYOCARDIUM; ADULTS AB Purpose:Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a distinctive 2-layered appearance of the myocardium because of increased trabeculation and deep intertrabecular recesses. Echocardiography serves as the initial noninvasive diagnostic test. Currently, magnetic resonance imaging (MRI) is increasingly being used to diagnose LVNC because of its improved temporal and spatial resolution. So far, no criteria have been proposed to define pathologic LVNC with the use of computed tomography (CT).Materials and Methods:We analyzed CT images using an American Heart Association 17-segment model in 8 patients previously diagnosed with LVNC by clinical diagnosis, echocardiography, and/or MRI, as well as in 11 patients with nonischemic dilated cardiomyopathy, 11 patients with hypertrophic cardiomyopathy, 10 patients with severe aortic stenosis, 9 patients with severe aortic regurgitation, 10 patients with left ventricular hypertrophy due to essential hypertension, and, additionally, in a control group of 20 patients who had normal CT scans without a history of cardiovascular disease. The distribution of LVNC was assessed by qualitative analysis of 17 myocardial segments for the presence or absence of any degree of noncompaction. Each segment was analyzed in each of the 3 end-diastolic long-axis views for the presence or absence of noncompaction, and the most prominent trabeculation was chosen for measurement. The left ventricular apex was excluded. Thickness of noncompacted and compacted myocardium was measured perpendicular to the compacted myocardium. The ratio of noncompacted to compacted (NC:C) myocardium was calculated for each segment. Receiver operating characteristics were used to generate cutoff values with sensitivity and specificity to distinguish the LVNC group from other groups.Results:An end-diastolic NC:C ratio >2.3 distinguished pathologic LVNC with 88% sensitivity and 97% specificity; positive and negative predictive values were 78% and 99%, respectively.Conclusions:CT using the standard MRI NC:C ratio cutoff >2.3 accurately characterizes pathologic LVNC. C1 [Sidhu, Manavjot S.; Uthamalingam, Shanmugam; Ahmed, Waleed; Engel, Leif-Christopher; Vorasettakarnkij, Yongkasem; Lee, Ashley M.; Hoffmann, Udo; Brady, Thomas; Abbara, Suhny; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Cardiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Sidhu, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Cardiol,Cardiac MRI PET CT Progra, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM manavsidhu83@gmail.com NR 17 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD JAN PY 2014 VL 29 IS 1 BP 60 EP 66 DI 10.1097/RTI.0b013e31828e9b3d PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 290HG UT WOS:000329744900010 PM 23689383 ER PT J AU Cooley, C Nishino, M Jagannathan, J Ramaiya, N Di Salvo, D Krajewski, KM AF Cooley, Christine Nishino, Mizuki Jagannathan, Jyothi Ramaiya, Nikhil Di Salvo, Donald Krajewski, Katherine M. TI Clinical Problem Solving Utility of Sonography in Oncologic Patients SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Review DE cancer; general sonography; radiology; sonography ID HEPATIC VENOOCCLUSIVE DISEASE; SURGICAL ADJUVANT BREAST; PORTAL-VEIN THROMBOSIS; FATTY LIVER-DISEASE; CANCER-PATIENTS; ABDOMINAL COMPLICATIONS; MARROW TRANSPLANTATION; ULTRASOUND EXAMINATION; BILIARY OBSTRUCTION; ACUTE CHOLECYSTITIS AB This review demonstrates the unique advantages of sonography in the oncologic setting. Although computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography are primary imaging modalities for evaluation of the oncologic patient, sonography is useful for evaluation of various conditions and clinical scenarios associated with cancer. The following article will illustrate the utility of sonography at a tertiary cancer center for diagnosis and problem solving. C1 [Cooley, Christine; Nishino, Mizuki; Jagannathan, Jyothi; Ramaiya, Nikhil; Di Salvo, Donald; Krajewski, Katherine M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Cooley, C (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM christinecooley@gmail.com FU National Institutes of Health [1K23CA157631]; Association of University Radiologists-General Electric Radiology Research Academic Fellowship (AUR-GERRAF) FX Dr Nishino was supported by National Institutes of Health grant 1K23CA157631. Dr Krajewski was supported by the Association of University Radiologists-General Electric Radiology Research Academic Fellowship (AUR-GERRAF). NR 53 TC 1 Z9 1 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD JAN PY 2014 VL 33 IS 1 BP 9 EP 22 DI 10.7863/ultra.33.1.9 PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 287JT UT WOS:000329538800003 PM 24371094 ER PT J AU Raudenska, M Gumulec, J Podlaha, O Sztalmachova, M Babula, P Eckschlager, T Adam, V Kizekb, R Masarik, M AF Raudenska, Martina Gumulec, Jaromir Podlaha, Ondrej Sztalmachova, Marketa Babula, Petr Eckschlager, Tomas Adam, Vojtech Kizekb, Rene Masarik, Michal TI Metallothionein polymorphisms in pathological processes SO METALLOMICS LA English DT Review ID METAL-RESPONSIVE ELEMENTS; SINGLE-NUCLEOTIDE POLYMORPHISMS; AMYOTROPHIC-LATERAL-SCLEROSIS; PROSTATE-SPECIFIC ANTIGEN; CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; GENE-EXPRESSION; IIA GENE; MAMMALIAN METALLOTHIONEIN; TRANSCRIPTION FACTOR AB Metallothioneins (MTs) are a class of metal-binding proteins characterized by a high cysteine content and low molecular weight. MTs play an important role in metal metabolism and protect cells against the toxic effects of radiation, alkylating agents and oxygen free radicals. The evidence that individual genetic characteristics of MTs play an important role in physiological and pathological processes associated with antioxidant defense and detoxification inspired targeted studies of genetic polymorphisms in a clinical context. In recent years, common MT polymorphisms were identified and associated with, particularly, western lifestyle diseases such as cancer, complications of atherosclerosis, and type 2 diabetes mellitus along with related complications. This review summarizes all evidence regarding MT polymorphisms of major human MTs (MT1, MT2, MT3 and MT4), their relation to pathological processes, and outlines specific applications of MTs as a set of genetic markers for certain pathologies. C1 [Raudenska, Martina; Gumulec, Jaromir; Sztalmachova, Marketa; Masarik, Michal] Masaryk Univ, Dept Pathol Physiol, Fac Med, CZ-62500 Brno, Czech Republic. [Raudenska, Martina; Gumulec, Jaromir; Adam, Vojtech; Kizekb, Rene; Masarik, Michal] Brno Univ Technol, Cent European Inst Technol, CZ-61600 Brno, Czech Republic. [Podlaha, Ondrej] Harvard Univ, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Sch Publ Hlth, Boston, MA 02115 USA. [Podlaha, Ondrej] Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA. [Sztalmachova, Marketa; Adam, Vojtech; Kizekb, Rene] Mendel Univ Brno, Dept Chem & Biochem, CZ-61300 Brno, Czech Republic. [Babula, Petr] Univ Vet & Pharmaceut Sci, Dept Nat Drugs, Fac Pharm, CZ-61242 Brno, Czech Republic. [Eckschlager, Tomas] Charles Univ Prague, Dept Paediat Haematol & Oncol, Fac Med 2, CZ-15006 Prague 5, Czech Republic. [Eckschlager, Tomas] Univ Hosp Motol, CZ-15006 Prague 5, Czech Republic. RP Masarik, M (reprint author), Masaryk Univ, Dept Pathol Physiol, Fac Med, Kamenice 5, CZ-62500 Brno, Czech Republic. EM masarik@med.muni.cz RI Gumulec, Jaromir/D-7638-2012; Masarik, Michal/D-9920-2012; Raudenska, Martina/F-9187-2012; Kizek, Rene/D-7748-2012; Sztalmachova, Marketa/F-4144-2012 OI Gumulec, Jaromir/0000-0002-9658-3444; FU CEITEC [CZ.1.05/1.1.00/02.0068, doc CEITEC.02/2012]; project for conceptual development of research organization [00064203] FX Financial support from CEITEC CZ.1.05/1.1.00/02.0068, doc CEITEC.02/2012 (JG), and project for conceptual development of research organization 00064203 is greatly acknowledged. NR 119 TC 34 Z9 34 U1 5 U2 51 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1756-5901 EI 1756-591X J9 METALLOMICS JI Metallomics PY 2014 VL 6 IS 1 BP 55 EP 68 DI 10.1039/c3mt00132f PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278LF UT WOS:000328891100004 PM 24068159 ER PT J AU Zhang, ZW Zhang, XM Newman, K Liu, XY Seth, P AF Zhang, Zhenwei Zhang, Xuemei Newman, Kam Liu, Xinyuan Seth, Prem TI MicroRNA Regulation of Oncolytic Adenovirus 6 for Selective Treatment of Castration- Resistant Prostate Cancer (vol 11, pg 2410, 2012) SO MOLECULAR CANCER THERAPEUTICS LA English DT Correction C1 [Zhang, Zhenwei; Newman, Kam; Seth, Prem] Univ Chicago, NorthShore Univ HealthSyst, Dept Med, Evanston, IL USA. [Zhang, Zhenwei; Liu, Xinyuan] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Zhang, Zhenwei; Zhang, Xuemei] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Nucl Med, Wuhan 430074, Peoples R China. [Liu, Xinyuan] Zhejiang Sci Tech Univ, Coll Life Sci, Xinyuan Inst Med & Biotechnol, Hangzhou, Zhejiang, Peoples R China. RP Zhang, ZW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM zhenwei_zhang@dfci.harvard.edu NR 2 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2014 VL 13 IS 1 BP 271 EP 271 DI 10.1158/1535-7163.MCT-13-0936 PG 1 WC Oncology SC Oncology GA 291GE UT WOS:000329815200028 ER PT J AU Polak, P Lawrence, MS Haugen, E Stoletzki, N Stojanov, P Thurman, RE Garraway, LA Mirkin, S Getz, G Stamatoyannopoulos, JA Sunyaev, SR AF Polak, Paz Lawrence, Michael S. Haugen, Eric Stoletzki, Nina Stojanov, Petar Thurman, Robert E. Garraway, Levi A. Mirkin, Sergei Getz, Gad Stamatoyannopoulos, John A. Sunyaev, Shamil R. TI Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair SO NATURE BIOTECHNOLOGY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; NUCLEASE-HYPERSENSITIVE SITES; SOMATIC MUTATIONS; CHROMATIN; DAMAGE; REGIONS; NUCLEOSOMES; EVOLUTION; MELANOMA; COMPLEX AB Carcinogenesis and neoplastic progression are mediated by the accumulation of somatic mutations. Here we report that the local density of somatic mutations in cancer genomes is highly reduced specifically in accessible regulatory DNA defined by DNase I hypersensitive sites. This reduction is independent of any known factors influencing somatic mutation density and is observed in diverse cancer types, suggesting a general mechanism. By analyzing individual cancer genomes(1), we show that the reduced local mutation density within regulatory DNA is linked to intact global genome repair machinery, with nearly complete abrogation of the hypomutation phenomenon in individual cancers that possess mutations in components of the nucleotide excision repair system. Together, our results connect chromatin structure, gene regulation and cancer-associated somatic mutation. C1 [Polak, Paz; Stoletzki, Nina; Sunyaev, Shamil R.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Polak, Paz; Stoletzki, Nina; Garraway, Levi A.; Sunyaev, Shamil R.] Harvard Univ, Sch Med, Boston, MA USA. [Polak, Paz; Lawrence, Michael S.; Stoletzki, Nina; Stojanov, Petar; Garraway, Levi A.; Getz, Gad; Sunyaev, Shamil R.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Haugen, Eric; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Haugen, Eric; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Mirkin, Sergei] Tufts Univ, Dept Biol, Medford, MA USA. RP Sunyaev, SR (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM jstam@u.washington.edu; ssunyaev@rics.bwh.harvard.edu OI Haugen, Eric/0000-0001-7444-8981 FU US National Institutes of Health (NIH) [U54CA143874, RO1MH101244, U54HG004592, HG007010] FX This work was supported by US National Institutes of Health (NIH) grants U54CA143874 and RO1MH101244 to S. R. S. and U54HG004592 and HG007010 to J.A.S. We thank D. Gordenin for his valuable feedback. NR 48 TC 30 Z9 30 U1 27 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2014 VL 32 IS 1 BP 71 EP + DI 10.1038/nbt.2778 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 287BM UT WOS:000329513000020 PM 24336318 ER PT J AU Anders, L Guenther, MG Qi, J Fan, ZP Marineau, JJ Rahl, PB Loven, J Sigova, AA Smith, WB Lee, TI Bradner, JE Young, RA AF Anders, Lars Guenther, Matthew G. Qi, Jun Fan, Zi Peng Marineau, Jason J. Rahl, Peter B. Loven, Jakob Sigova, Alla A. Smith, William B. Lee, Tong Ihn Bradner, James E. Young, Richard A. TI Genome-wide localization of small molecules SO NATURE BIOTECHNOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; SELECTIVE-INHIBITION; GENE-EXPRESSION; DRUG DISCOVERY; C-MYC; CHROMATIN; TARGET; LEUKEMIA; CANCER; BROMODOMAINS AB A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods will be broadly useful to enhance understanding of therapeutic action and to characterize the specificity of chemical entities that interact with DNA or genome-associated proteins. C1 [Anders, Lars; Guenther, Matthew G.; Fan, Zi Peng; Rahl, Peter B.; Loven, Jakob; Sigova, Alla A.; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Qi, Jun; Marineau, Jason J.; Smith, William B.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Fan, Zi Peng] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Young, Richard A.] MIT, Dept Biol, Cambridge, MA USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM james_bradner@dfci.harvard.edu; young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU US National Institutes of Health [HG002668, CA109901, CA146445]; Swedish Research Council [VR-B0086301]; American Cancer Society [PF-11-042-01-DMC]; Leukemia & Lymphoma Society; Damon-Runyon Cancer Research Foundation FX We thank T. Volkert, J. Love, J.-A. Kwon and S. Gupta at the Whitehead Genome Technology Core for Solexa sequencing, E. Cohick for help with cell culture, and A. Federation and R. St. Pierre at the Dana-Farber Cancer Institute for biochemistry support. This work was supported by US National Institutes of Health grants HG002668 (R.A.Y.), CA109901 (R.A.Y.) and CA146445 (R.A.Y., T. I. L.), Swedish Research Council Postdoctoral Fellowship VR-B0086301 (J. L.), American Cancer Society Postdoctoral Fellowship PF-11-042-01-DMC (P. B. R.), the Leukemia & Lymphoma Society (J. Q. and J. E. B.) and the Damon-Runyon Cancer Research Foundation (J.E.B.). NR 43 TC 50 Z9 50 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2014 VL 32 IS 1 BP 92 EP + DI 10.1038/nbt.2776 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 287BM UT WOS:000329513000023 PM 24336317 ER PT J AU Akshoomoff, N Newman, E Thompson, WK McCabe, C Bloss, CS Chang, L Amaral, DG Casey, BJ Ernst, TM Frazier, JA Gruen, JR Kaufmann, WE Kenet, T Kennedy, DN Libiger, O Mostofsky, S Murray, SS Sowell, ER Schork, N Dale, AM Jernigan, TL AF Akshoomoff, Natacha Newman, Erik Thompson, Wesley K. McCabe, Connor Bloss, Cinnamon S. Chang, Linda Amaral, David G. Casey, B. J. Ernst, Thomas M. Frazier, Jean A. Gruen, Jeffrey R. Kaufmann, Walter E. Kenet, Tal Kennedy, David N. Libiger, Ondrej Mostofsky, Stewart Murray, Sarah S. Sowell, Elizabeth R. Schork, Nicholas Dale, Anders M. Jernigan, Terry L. CA Pediat Imaging Neurocognition TI The NIH Toolbox Cognition Battery: Results From a Large Normative Developmental Sample (PING) SO NEUROPSYCHOLOGY LA English DT Article DE computerized assessment; cognitive development; socioeconomic status ID NORMAL BRAIN-DEVELOPMENT; POPULATION-BASED SAMPLE; EXECUTIVE FUNCTION; NEUROPSYCHOLOGICAL BATTERY; SOCIOECONOMIC-STATUS; HEALTHY-CHILDREN; HUMAN GENOME; PERFORMANCE; ATTENTION; RELIABILITY AB Objective: The NIH Toolbox Cognition Battery (NTCB) was designed to provide a brief, efficient computerized test of key neuropsychological functions appropriate for use in children as young as 3 years of age. This report describes the performance of a large group of typically developing children and adolescents and examines the impact of age and sociocultural variables on test performance. Method: The NTCB was administered to a sample of 1,020 typically developing males and females ranging in age from 3 to 20 years, diverse in terms of socioeconomic status (SES) and race/ethnicity, as part of the new publicly accessible Pediatric Imaging, Neurocognition, and Genetics (PING) data resource, at 9 sites across the United States. Results: General additive models of nonlinear age-functions were estimated from age-differences in test performance on the 8 NTCB subtests while controlling for family SES and genetic ancestry factors (GAFs). Age accounted for the majority of the variance across all NTCB scores, with additional significant contributions of gender on some measures, and of SES and race/ethnicity (GAFs) on all. After adjusting for age and gender, SES and GAFs explained a substantial proportion of the remaining unexplained variance in Picture Vocabulary scores. Conclusions: The results highlight the sensitivity to developmental effects and efficiency of this new computerized assessment battery for neurodevelopmental research. Limitations are observed in the form of some ceiling effects in older children, some floor effects, particularly on executive function tests in the youngest participants, and evidence for variable measurement sensitivity to cultural/socioeconomic factors. C1 [Akshoomoff, Natacha; Newman, Erik; Thompson, Wesley K.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Akshoomoff, Natacha; Newman, Erik; McCabe, Connor] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA. [Thompson, Wesley K.] Univ Calif San Diego, Stein Inst Res Aging, La Jolla, CA 92093 USA. [Bloss, Cinnamon S.; Libiger, Ondrej; Murray, Sarah S.; Schork, Nicholas] Scripps Translat Sci Inst, Scripps Genom Med, La Jolla, CA USA. [Bloss, Cinnamon S.; Libiger, Ondrej; Murray, Sarah S.; Schork, Nicholas] Scripps Hlth, La Jolla, CA USA. [Chang, Linda; Ernst, Thomas M.] Univ Hawaii, Dept Med, Honolulu, HI 96822 USA. [Chang, Linda; Ernst, Thomas M.] Queens Med Ctr, Honolulu, HI USA. [Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Amaral, David G.] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Casey, B. J.] Weill Cornell Med Coll, Sackler Inst Dev Psychobiol, New York, NY USA. [Frazier, Jean A.; Kennedy, David N.] Univ Massachusetts Med Sch, Dept Psychiat, Worcester, MA USA. [Gruen, Jeffrey R.] Yale Univ Sch Med, Dept Pediat, New Haven, CT USA. [Gruen, Jeffrey R.] Yale Univ Sch Med, Dept Genet, New Haven, CT USA. [Kaufmann, Walter E.; Mostofsky, Stewart] Kennedy Krieger Inst, Baltimore, MD USA. [Kaufmann, Walter E.; Mostofsky, Stewart] Johns Hopkins Univ Sch Med, Baltimore, MD USA. [Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Kenet, Tal] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sowell, Elizabeth R.] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Sowell, Elizabeth R.] Childrens Hosp, Los Angeles, CA 90027 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Dale, Anders M.; Jernigan, Terry L.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA. [Jernigan, Terry L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, San Diego, CA 92103 USA. RP Akshoomoff, N (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM nakshoomoff@ucsd.edu FU NCATS NIH HHS [UL1 TR001079]; NICHD NIH HHS [P30 HD004147, P30 HD018655]; NIDA NIH HHS [RC2 DA029475, RC2DA029475]; NIMH NIH HHS [P30 MH062512, R01 MH083320] NR 40 TC 21 Z9 21 U1 4 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2014 VL 28 IS 1 BP 1 EP 10 DI 10.1037/neu0000001 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 281RO UT WOS:000329118900001 PM 24219608 ER PT J AU Guo, FJ Moellering, DR Garvey, WT AF Guo, Fangjian Moellering, Douglas R. Garvey, W. Timothy TI The progression of cardiometabolic disease: Validation of a new cardiometabolic disease staging system applicable to obesity SO OBESITY LA English DT Article ID CORONARY-HEART-DISEASE; TREATMENT PANEL-III; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; WEIGHT-LOSS; FOLLOW-UP; RISK AB Objective To validate a Cardiometabolic Disease Staging (CMDS) system for assigning risk level for diabetes, and all-cause and cardiovascular disease (CVD) mortality. Design and Methods Two large national cohorts, CARDIA and NHANES III, were used to validate CMDS. CMDS: Stage 0: metabolically healthy; Stage 1: one or two metabolic syndrome risk factors [other than impaired fasting glucose (IFG)]; Stage 2: IFG or impaired glucose tolerance (IGT) or metabolic syndrome (without IFG); Stage 3: two of three (IFG, IGT, and/or metabolic syndrome); and Stage 4: type 2 diabetes mellitus/CVD. Results In the CARDIA study, compared with Stage 0 metabolically healthy subjects, adjusted risk for diabetes exponentially increased from Stage 1 [hazard ratio (HR) 2.83, 95% confidence interval (CI): 1.76-4.55], to Stage 2 (HR 8.06, 95% CI 4.91-13.2), to Stage 3 (HR 23.5, 95% CI 13.7-40.1) (P for trend <0.001). In NHANES III, both cumulative incidence and multivariable adjusted HRs markedly increased for both all-cause and CVD mortality with advancement of the risk stage from Stages 0 to 4. Adjustment for body mass index (BMI) minimally affected the risks for diabetes and all-cause/CVD mortality using CMDS. Conclusion CMDS can discriminate a wide range of risk for diabetes, CVD mortality, and all-cause mortality independent of BMI, and should be studied as a risk assessment tool to guide interventions that prevent and treat cardiometabolic disease. C1 [Guo, Fangjian; Moellering, Douglas R.; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Guo, FJ (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. EM ilovedd@uab.edu; garveyt@uab.edu RI Guo, Fangjian/B-7705-2015 OI Guo, Fangjian/0000-0003-3729-2724 FU Merit Review program of the Department of Veterans Affairs; National Institutes of Health [DK-038765, DK-083562]; UAB Diabetes Research Center [P60-DK079626] FX The Merit Review program of the Department of Veterans Affairs, National Institutes of Health (DK-038765 and DK-083562), and the UAB Diabetes Research Center (P60-DK079626). NR 37 TC 17 Z9 19 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JAN PY 2014 VL 22 IS 1 BP 110 EP 118 DI 10.1002/oby.20585 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 288LN UT WOS:000329613600020 PM 23894121 ER PT J AU McCarthy, JF Ilgen, MA Austin, K Blow, FC Katz, IR AF McCarthy, John F. Ilgen, Mark A. Austin, Karen Blow, Frederic C. Katz, Ira R. TI Associations between body mass index and suicide in the veterans affairs health system SO OBESITY LA English DT Article ID DEATH REPORTING SYSTEM; GENERAL-POPULATION; DEPRESSIVE SYMPTOMS; COMPLETED SUICIDE; RISK-FACTORS; US ADULTS; OBESITY; OVERWEIGHT; MEN; MORTALITY AB Objectives Associations between BMI and suicide risks and methods for individuals receiving care in the Veterans Health Administration (VHA) health system were evaluated. Design and Methods For 4,005,640 patients in fiscal years 2001-2002, multivariable survival analyses assessed associations between BMI and suicide, through FY2009. Covariates included demographics, psychiatric, and nonpsychiatric diagnoses, receipt of VHA mental health encounters, and regional network. Among suicide decedents, multivariable Generalized Estimating Equations (GEE) regression examined associations between BMI and suicide method. Results 1.3% of patients were underweight, 24.3% normal weight, 40.6% overweight, and 33.8% obese. Underweight was associated with increased suicide risk (adjusted hazard ratio [AHR] = 1.17, 95% CI: 1.01, 1.36) compared to normal. Overweight and obese status were associated with lower risk (AHR = 0.78, 95% CI: 0.74, 0.82; AHR = 0.63, 95% CI: 0.60, 0.66, respectively). Among suicide decedents, high lethality methods were most common among underweight and least common among obese individuals. Adjusting for covariates, BMI was not associated with method lethality, yet some associations were observed between BMI and specific methods. Conclusion Among VHA patients, BMI was negatively associated with suicide risks. These differences may partly relate to choice of suicide method. Low BMI offers an additional resource for clinical suicide risk assessments. C1 [McCarthy, John F.; Ilgen, Mark A.; Austin, Karen; Blow, Frederic C.; Katz, Ira R.] US Dept Vet Affairs, Off Mental Hlth Operat, Washington, DC 20420 USA. [McCarthy, John F.; Ilgen, Mark A.; Blow, Frederic C.] VA OMHO Serious Mental Illness Treatment Resource, Ann Arbor, MI USA. [McCarthy, John F.; Ilgen, Mark A.; Austin, Karen; Blow, Frederic C.] VA Ctr Clin Management Res, Washington, DC USA. [McCarthy, John F.; Ilgen, Mark A.; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP McCarthy, JF (reprint author), US Dept Vet Affairs, Off Mental Hlth Operat, Washington, DC 20420 USA. EM john.mccarthy2@va.gov NR 40 TC 6 Z9 7 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JAN PY 2014 VL 22 IS 1 BP 269 EP 276 DI 10.1002/oby.20422 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 288LN UT WOS:000329613600039 PM 23512622 ER PT J AU Frelinger, AL Jakubowski, JA Brooks, JK Carmichael, SL Berny-Lang, MA Barnard, MR Heeney, MM Michelson, AD AF Frelinger, Andrew L., III Jakubowski, Joseph A. Brooks, Julie K. Carmichael, Sabrina L. Berny-Lang, Michelle A. Barnard, Marc R. Heeney, Matthew M. Michelson, Alan D. TI Platelet Activation and Inhibition iN Sickle cell disease (PAINS) study SO PLATELETS LA English DT Article DE Platelets; prasugrel; sickle cell disease ID PULMONARY-HYPERTENSION; ANTIPLATELET AGENT; ACTIVE METABOLITE; P-SELECTIN; ASPIRIN; PRASUGREL; INFLAMMATION; PROPHYLAXIS; HEMOGLOBIN; HEMOLYSIS AB Platelet activation/ aggregation in sickle cell disease (SCD) may promote tissue ischemia, suggesting that antiplatelet therapy may be useful. However, the assessment of platelet function and the effect of antiplatelet therapy in blood from SCD patients may be confounded by hemolysis with the release of adenosine 50-diphosphate (ADP). Here we evaluate the levels of platelet activation markers in SCD adolescents vs. normal controls and compare, by multiple methods, the effect of in vitro blockade of the platelet ADP receptor P2Y(12) by prasugrel's active metabolite, R-138727. Platelet activation markers in blood from SCD adolescents (n = 15) and healthy adults (n = 10), and the effect of R-138727 (0.1-10 mu M) added in vitro, were evaluated with and without ADP stimulation. The circulating levels of platelet-monocyte and plateletneutrophil aggregates were significantly higher (p< 0.01) in SCD patients than in healthy controls. R-138727, in a concentration-dependent manner, inhibited platelet function in both SCD patients and healthy subjects as judged by ADP-stimulated light transmission aggregation, VerifyNow (R) P2Y12 assay, multiple electrode aggregometry, and flow cytometric analysis of platelet vasodilator-stimulated phosphoprotein, activated GPIIb-IIIa and P-selectin. The R-138727 IC(50)s for each assay were not significantly different in SCD vs. healthy subjects. In summary: (1) The high circulating levels of platelet-monocyte and platelet-neutrophil aggregates demonstrate in vivo platelet activation in SCD and may be useful as markers of the in vivo pharmacodynamic efficacy of antiplatelet therapy in SCD. (2) The similar in vitro R-138727 IC(50)s in SCD and healthy subjects suggest that the prasugrel dose-dependence for platelet inhibition in SCD patients will be similar to that previously observed in healthy subjects. C1 [Frelinger, Andrew L., III; Brooks, Julie K.; Carmichael, Sabrina L.; Berny-Lang, Michelle A.; Barnard, Marc R.; Heeney, Matthew M.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Boston, Boston, MA 02115 USA. [Jakubowski, Joseph A.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Barnard, Marc R.] Univ Massachusetts, Sch Med, Flow Cytometry Core Facil, Worcester, MA USA. RP Frelinger, AL (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Ctr Platelet Res Studies, Karp 07212,300 Longwood Ave, Boston, MA 02115 USA. EM andrew.frelinger@childrens.harvard.edu RI Heeney, Matthew/J-6838-2015 OI Heeney, Matthew/0000-0002-1104-6843 FU Eli Lilly and Company; Boston Children's Hospital FX This study was funded in part by a grant from Eli Lilly and Company and Daiichi Sankyo to Boston Children's Hospital (Principal Investigator: A. L. Frelinger III). A. L. Frelinger and A. D. Michelson have been investigators on research grants to Boston Children's Hospital from GLSynthesis and Eli Lilly. Dr. Michelson has been a member of the Data Monitoring Committee of a clinical trial sponsored by Lilly. J.A. Jakubowski is an employee and shareholder of Eli Lilly and Company. M. M. Heeney has been a consultant to Eli Lilly. J.K. Brooks, S. L. Carmichael, M. A. Berny-Lang, and M. R. Barnard report no conflicts. NR 28 TC 11 Z9 11 U1 0 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PY 2014 VL 25 IS 1 BP 27 EP 35 DI 10.3109/09537104.2013.770136 PG 9 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 291XF UT WOS:000329865000005 PM 23469943 ER PT J AU Metraux, S Stino, M Culhane, DP AF Metraux, Stephen Stino, Magdi Culhane, Dennis P. TI Validation of Self-Reported Veteran Status Among Two Sheltered Homeless Populations SO PUBLIC HEALTH REPORTS LA English DT Article ID INDIVIDUALS; TRUST AB Objectives. We assessed the accuracy of self-reported veteran status among sheltered homeless adults to assess the reliability of using self-report to determine the number of veterans in homeless populations and examine whether there are demographic correlates to inaccurate reporting of veteran status. Methods. Records on 5,860 sheltered adults from Columbus, Ohio, and 16,346 sheltered adults from New York City (NYC) were matched with U.S. Department of Veterans Affairs (VA) records. We analyzed the agreement between veteran,self-reporting and official records using descriptive measures, diagnostic tests, and logistic regression. Results. The degree of concordance was moderate. Using VA records rather than self-report data to determine veteran status increased homeless veteran prevalence rates by 27% in Columbus and 39% in NYC. Veterans with discordant veteran status (i.e., false positive or false negative) showed lower levels of services use in the VA (both cities) and in the municipal shelter system (NYC only). Younger veterans and women were at higher risk of not being identified as veterans. Conclusion. Administrative records can help to more accurately identify homeless veterans and to connect them to available services and benefits. C1 [Metraux, Stephen; Stino, Magdi; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19104 USA. [Metraux, Stephen; Stino, Magdi] Allegheny Univ Hlth Sci, Dept Hlth Policy & Publ Hlth, Philadelphia, PA 19102 USA. [Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Metraux, S (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4101 Chester Ave, Philadelphia, PA 19104 USA. EM stephen.metraux@va.gov NR 23 TC 1 Z9 1 U1 0 U2 3 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2014 VL 129 IS 1 BP 73 EP 77 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 288BL UT WOS:000329586900010 PM 24381362 ER PT J AU Brent, BK Seidman, LJ Thermenos, HW Holt, DJ Keshavan, MS AF Brent, Benjamin K. Seidman, Larry J. Thermenos, Heidi W. Holt, Daphne J. Keshavan, Matcheri S. TI Self-disturbances as a possible premorbid indicator of schizophrenia risk: A neurodevelopmental perspective SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Self-disturbances; Schizophrenia; Premorbid; Genetic high-risk; Neurodevelopment ID ULTRA-HIGH-RISK; CHILDHOOD-ONSET SCHIZOPHRENIA; FUNCTIONAL CONNECTIVITY MRI; MEDIAL PREFRONTAL CORTEX; GREY-MATTER CHANGES; GENETIC HIGH-RISK; DEFAULT-MODE; NONPSYCHOTIC SIBLINGS; WORKING-MEMORY; BRAIN-FUNCTION AB Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the "neural circuitry of self" may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that "early" (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), and parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of "self" during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal-parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia. (C) 2013 Elsevier B.V. All rights reserved. C1 [Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Holt, Daphne J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Keshavan, Matcheri S.] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Holt, Daphne J.; Keshavan, Matcheri S.] Harvard Univ, Sch Med, Boston, MA USA. RP Brent, BK (reprint author), Beth Israel Deaconess Med Ctr, Dept Psychiat, 330 Brookline Ave, Boston, MA 02215 USA. EM bbrent@bidmc.harvard.edu FU Harvard Catalyst; Harvard Clinical and Translational Science Center, NIH [KL2 RR 025757]; Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; NIMH [RO1 64023, RO1 78113, K02 01180] FX This project was supported in part by a KL2 Medical Research Investigator Training (MeRIT) award from the Harvard Catalyst and The Harvard Clinical and Translational Science Center, NIH KL2 RR 025757 (BKB), the Commonwealth Research Center of the Massachusetts Department of Mental Health, SCDMH82101008006 (LJS), and by NIMH RO1 64023, RO1 78113, and K02 01180 (MKS). NR 141 TC 24 Z9 24 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2014 VL 152 IS 1 BP 73 EP 80 DI 10.1016/j.schres.2013.07.038 PG 8 WC Psychiatry SC Psychiatry GA 283AR UT WOS:000329217000011 PM 23932148 ER PT J AU Perlstein, MD Chohan, MR Coman, IL Antshel, KM Fremont, WP Gnirke, MH Kikinis, Z Middleton, FA Radoeva, PD Shenton, ME Kates, WR AF Perlstein, Matthew D. Chohan, Moeed R. Coman, Ioana L. Antshel, Kevin M. Fremont, Wanda P. Gnirke, Matthew H. Kikinis, Zora Middleton, Frank A. Radoeva, Petya D. Shenton, Martha E. Kates, Wendy R. TI White matter abnormalities in 22q11.2 deletion syndrome: Preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Velo-cardio-facial syndrome; RTN4R gene; rs701428; Diffusion tensor imaging (DTI); Anterior limb of internal capsule; Uncinate fasciculus ID CARDIO-FACIAL SYNDROME; NONSPATIAL WORKING-MEMORY; VELOCARDIOFACIAL SYNDROME; UNCINATE FASCICULUS; CHROMOSOME 22Q11.2; AXIAL DIFFUSIVITY; INTERNAL CAPSULE; CAUDATE-NUCLEUS; ANTERIOR LIMB; AXON GROWTH AB Background: This study utilized diffusion tensor imaging (DTI) to analyze white matter tractography in the anterior limb of the internal capsule (ALIC), fornix, and uncinate fasciculus (UF) of individuals with 22q11.2 deletion syndrome and controls. Aberrations in these tracts have been previously associated with schizophrenia. With up to 25% of individuals with 22q11.2DS developing schizophrenia in adulthood, we hypothesized reduction in structural integrity of these tracts, including an association with prodromal symptoms of psychosis. We further predicted an association between allelic variation in a functional polymorphism of the Nogo-66 receptor gene and 22q11.2DS white matter integrity. Methods: Tractography was conducted using fiber assignment by streamline tracking algorithm in DTI Studio. Subjects were genotyped for the rs701428 SNP of the Nogo-66 receptor gene, and assessed for presence of prodromal symptoms. Results: We found significant group differences between 22q11.2DS and controls in DTI metrics for all three tracts. DTI metrics of ALIC and UF were associated with prodromal symptoms in 22q11.2DS. Further, ALIC DTI metrics were associated with allelic variation of the rs701428 SNP of the Nogo-66 receptor gene in 22q11.2DS. Conclusions: Alterations in DTI metrics suggest white matter microstructural anomalies of the ALIC, fornix, and UF in 22q11.2DS. Structural differences in ALIC appear to be associated with the Nogo-66 receptor gene, which has been linked to myelin-mediated axonal growth inhibition. Moreover, the association between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66 receptor gene may represent a susceptibility gene for psychosis through its disruption of white matter microstructure and myelin-associated axonal growth. (C) 2013 Elsevier B.V. All rights reserved. C1 [Perlstein, Matthew D.; Chohan, Moeed R.; Coman, Ioana L.; Antshel, Kevin M.; Fremont, Wanda P.; Gnirke, Matthew H.; Middleton, Frank A.; Radoeva, Petya D.; Kates, Wendy R.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Middleton, Frank A.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Antshel, Kevin M.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Kikinis, Zora; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Clin Neurosci Div,Neurosci Lab,Dept Psychiat, Boston, MA 02115 USA. RP Kates, WR (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. EM katesw@upstate.edu OI kikinis, zora/0000-0002-7203-1362; Chohan, Moeed/0000-0003-4802-2666; Shenton, Martha/0000-0003-4235-7879 FU National Institutes of Health [MH064824]; Golisano Children's Hospital FX This work was supported by funding from the National Institutes of Health (MH064824) and the Golisano Children's Hospital, both to WRK. We also acknowledge the assistance of Cynthia Salazar who processed the DNA. NR 67 TC 11 Z9 11 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2014 VL 152 IS 1 BP 117 EP 123 DI 10.1016/j.schres.2013.11.015 PG 7 WC Psychiatry SC Psychiatry GA 283AR UT WOS:000329217000017 PM 24321711 ER PT J AU Ohtani, T Levitt, JJ Nestor, PG Kawashima, T Asami, T Shenton, ME Niznikiewicz, M McCarley, RW AF Ohtani, Toshiyuki Levitt, James J. Nestor, Paul G. Kawashima, Toshiro Asami, Takeshi Shenton, Martha E. Niznikiewicz, Margaret McCarley, Robert W. TI Prefrontal cortex volume deficit in schizophrenia: A new look using 3 T MRI with manual parcellation SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Magnetic resonance imaging; Prefrontal cortex; Negative symptom; Cognitive switching ID COGNITIVE IMPAIRMENT; NEGATIVE SYMPTOMS; VERBAL FLUENCY; BRAIN; PERFORMANCE; DISORDER; GYRUS; EMOTION; LESIONS AB In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3 T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p = 0.004), bilateral MFG (left: p = 0.007; right: p = 0.007), and bilateral IFG (left: p < 0.001; right: p = 0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R = -0.465, p = 0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R = 0.440, p = 0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching. (C) 2013 Elsevier B.V. All rights reserved. C1 [Ohtani, Toshiyuki; Levitt, James J.; Nestor, Paul G.; Kawashima, Toshiro; Asami, Takeshi; Shenton, Martha E.; Niznikiewicz, Margaret; McCarley, Robert W.] Boston Healthcare Syst, Dept Psychiat, Neurosci Lab, Clin Neurosci Div,VA,Brockton Div, Boston, MA 02301 USA. [Ohtani, Toshiyuki; Levitt, James J.; Nestor, Paul G.; Kawashima, Toshiro; Asami, Takeshi; Shenton, Martha E.; Niznikiewicz, Margaret; McCarley, Robert W.] Harvard Univ, Sch Med, Boston, MA 02301 USA. [Ohtani, Toshiyuki; Levitt, James J.; Kawashima, Toshiro; Asami, Takeshi; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Ohtani, Toshiyuki] Chiba Univ, Chiba 2638522, Japan. [Nestor, Paul G.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Kawashima, Toshiro] Saga Univ Hosp, Dept Psychiat, Saga 8498501, Japan. [Asami, Takeshi] Yokohama City Univ Med, Dept Psychiat, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. RP Ohtani, T (reprint author), Chiba Univ, Inage Ku, 1-33 Yayoicho, Chiba 2638522, Japan. EM otanit@chiba-u.jp RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Dept. of Veterans Affairs Medical Research Division [Schizophrenia Center]; Dept. of Veterans Affairs Medical Research Division [Merit Awards]; National Institute of Mental Health [K02 MH 01110, R01MH50747, R01MH40799, R01 MH 052807, CIDAR 1P50MH080272-01] FX This study was supported by the Dept. of Veterans Affairs Medical Research Division [Schizophrenia Center (Drs. McCarley, Shenton), Merit Awards to Drs. McCarley, Shenton and Levitt] and by grants K02 MH 01110 and R01MH50747 (Dr. Shenton), R01MH40799 and R01 MH 052807 (Dr. McCarley), and CIDAR 1P50MH080272-01 (Dr. McCarley) from the National Institute of Mental Health. NR 40 TC 9 Z9 10 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2014 VL 152 IS 1 BP 184 EP 190 DI 10.1016/j.schres.2013.10.026 PG 7 WC Psychiatry SC Psychiatry GA 283AR UT WOS:000329217000027 PM 24280350 ER PT J AU Proal, AC Fleming, J Galvez-Buccollini, JA DeLisi, LE AF Proal, Ashley C. Fleming, Jerry Galvez-Buccollini, Juan A. DeLisi, Lynn E. TI A controlled family study of cannabis users with and without psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article ID O-METHYLTRANSFERASE GENE; USE DISORDERS; SCHIZOPHRENIA; POLYMORPHISM; ONSET; ASSOCIATION; RELATIVES; SYMPTOMS; RISK; AGE AB Background: Cannabis is one of the most highly abused illicit drugs in the world. Several studies suggest a link between adolescent cannabis use and schizophrenia. An understanding of this link would have significant implications for legalization of cannabis and its medicinal value. The present study aims to determine whether familial morbid risk for schizophrenia is the crucial factor that underlies the association of adolescent cannabis use with the development of schizophrenia. Methods: Consecutively obtained probands were recruited into four samples: sample 1: 87 non-psychotic controls with no drug use; sample 2: 84 non-psychotic controls with cannabis use; sample 3: 32 patients with a schizophrenia spectrum psychosis with no drug use; sample 4: 76 patients with schizophrenia spectrum psychosis with cannabis use. All cannabis using subjects used this drug during adolescence, and no other substance, with the exception of alcohol. Structured interviews of probands and family informants were used to obtain diagnostic information about probands and all their known relatives. Results: There was an increased morbid risk for schizophrenia in relatives of the cannabis using and non-using patient samples compared with their respective non-psychotic control samples (p = .002, p < .001 respectively). There was no significant difference in morbid risk for schizophrenia between relatives of the patients who use or do not use cannabis (p = .43). Conclusions: The results of the current study suggest that having an increased familial morbid risk for schizophrenia may be the underlying basis for schizophrenia in cannabis users and not cannabis use by itself. Published by Elsevier B.V. C1 [Proal, Ashley C.; Fleming, Jerry; Galvez-Buccollini, Juan A.; DeLisi, Lynn E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fleming, Jerry; Galvez-Buccollini, Juan A.; DeLisi, Lynn E.] Vet Adm Boston Healthcare Syst, Brockton, MA 02301 USA. RP DeLisi, LE (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA USA. EM Lynn_DeLisi@hms.harvard.edu FU National Institute of Drug Abuse [R01 DA 021576] FX This project was funded by the National Institute of Drug Abuse (R01 DA 021576). NR 20 TC 17 Z9 17 U1 1 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2014 VL 152 IS 1 BP 283 EP 288 DI 10.1016/j.schres.2013.11.014 PG 6 WC Psychiatry SC Psychiatry GA 283AR UT WOS:000329217000041 PM 24309013 ER PT J AU van Erp, TGM Preda, A Nguyen, D Faziola, L Turner, J Bustillo, J Belger, A Lim, KO McEwen, S Voyvodic, J Mathalon, DH Ford, J Potkin, SG AF van Erp, Theo G. M. Preda, Adrian Dana Nguyen Faziola, Lawrence Turner, Jessica Bustillo, Juan Belger, Aysenil Lim, Kelvin O. McEwen, Sarah Voyvodic, James Mathalon, Daniel H. Ford, Judith Potkin, Steven G. CA FBIRN TI Converting positive and negative symptom scores between PANSS and SAPS/SANS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Symptoms; Marder; Conversion; Meta; Multi-center ID SYNDROME-SCALE; RATING-SCALE; SCHIZOPHRENIA; DIMENSIONS; RECOMMENDATIONS; RELIABILITY; VALIDATION; TRIALS; MODEL AB The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) are the most widely used schizophrenia symptom rating scales, but despite their co-existence for 25 years no easily usable between-scale conversion mechanism exists. The aim of this study was to provide equations for between-scale symptom rating conversions. Two-hundred-and-five schizophrenia patients [mean age +/- SD = 39.5 +/- 11.6, 156 males] were assessed with the SANS, SAPS, and PANSS. Pearson's correlations between symptom scores from each of the scales were computed. Linear regression analyses, on data from 176 randomly selected patients, were performed to derive equations for converting ratings between the scales. Intraclass correlations, on data from the remaining 29 patients, not part of the regression analyses, were performed to determine rating conversion accuracy. Between-scale positive and negative symptom ratings were highly correlated. Intraclass correlations between the original positive and negative symptom ratings and those obtained via conversion of alternative ratings using the conversion equations were moderate to high (ICCs = 0.65 to 0.91). Regression-based equations may be useful for conversion between schizophrenia symptom severity as measured by the SANS/SAPS and PANSS, though additional validation is warranted. This study's conversion equations, implemented at http:/converteasy.org, may aid in the comparison of medication efficacy studies, in meta- and mega-analyses examining symptoms as moderator variables, and in retrospective combination of symptom data in multi-center data sharing projects that need to pool symptom rating data when such data are obtained using different scales. (C) 2013 Elsevier B.V. All rights reserved. C1 [van Erp, Theo G. M.; Preda, Adrian; Dana Nguyen; Faziola, Lawrence; Potkin, Steven G.; FBIRN] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA. [Turner, Jessica] Mind Res Network, Albuquerque, NM 87106 USA. [Turner, Jessica; Bustillo, Juan] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Turner, Jessica; Bustillo, Juan] Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Belger, Aysenil] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Lim, Kelvin O.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55454 USA. [McEwen, Sarah] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Voyvodic, James] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Mathalon, Daniel H.; Ford, Judith] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Mathalon, Daniel H.; Ford, Judith] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. RP van Erp, TGM (reprint author), Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, 5251 Calif Ave,Suite 240C, Irvine, CA 92617 USA. RI Turner, Jessica/H-7282-2015; Preda, Adrian /K-8889-2013; Faziola, Lawrence/P-7686-2014; OI Turner, Jessica/0000-0003-0076-8434; Preda, Adrian /0000-0003-3373-2438; Faziola, Lawrence/0000-0002-0376-3586; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974; Potkin, Steven/0000-0003-1028-1013 FU National Center for Research Resources at the National Institutes of Health [NIH 1 U24 U24 RR021992]; National Institutes of Health (NIH) [1 U24 RR025736-01] FX This work was supported by the National Center for Research Resources at the National Institutes of Health (grant numbers: NIH 1 U24 U24 RR021992 (Function Biomedical Informatics Research Network) and National Institutes of Health (NIH) 1 U24 RR025736-01 (Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org). NR 34 TC 13 Z9 13 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2014 VL 152 IS 1 BP 289 EP 294 DI 10.1016/j.schres.2013.11.013 PG 6 WC Psychiatry SC Psychiatry GA 283AR UT WOS:000329217000042 PM 24332632 ER PT J AU Ishida, JH Johansen, KL AF Ishida, Julie H. Johansen, Kirsten L. TI Iron and Infection in Hemodialysis Patients SO SEMINARS IN DIALYSIS LA English DT Review ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; INTRAVENOUS IRON; POLYMORPHONUCLEAR LEUKOCYTES; MAINTENANCE HEMODIALYSIS; DIALYSIS PATIENTS; FERRIC GLUCONATE; YERSINIA-ENTEROCOLITICA; BACTERICIDAL FUNCTION; PRACTICE GUIDELINES AB Intravenous iron is an important component of the treatment of anemia of end-stage renal disease (ESRD), but it is biologically plausible that iron could increase the risk of infection through impairment of neutrophil and T-cell function and promotion of microbial growth. Any such increase in risk would be particularly important because infection is a significant cause of mortality and morbidity in dialysis patients. The overall evidence favors an association between iron and infection in hemodialysis patients, but the optimal iron management strategy to minimize infection risk has yet to be identified. There is a need for further research on this topic, particularly in light of increased utilization of intravenous iron following implementation of the bundled ESRD reimbursement system. C1 [Ishida, Julie H.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Dept Med, Div Nephrol, San Francisco, CA USA. RP Ishida, JH (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, Box 0532,521 Parnassus Ave,Clin Sci C443, San Francisco, CA 94143 USA. EM julie.ishida@ucsf.edu FU American Society of Nephrology; NIDDK [K24DK085153] FX Dr. Ishida is supported by the American Society of Nephrology Dr. Johansen is supported by the NIDDK (K24DK085153). NR 78 TC 16 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN PY 2014 VL 27 IS 1 BP 26 EP 36 DI 10.1111/sdi.12168 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 286XH UT WOS:000329502100013 PM 24329610 ER PT J AU Grandner, MA Chakravorty, S Perlis, ML Oliver, L Gurubhagavatula, I AF Grandner, Michael A. Chakravorty, Subhajit Perlis, Michael L. Oliver, Linden Gurubhagavatula, Indira TI Habitual sleep duration associated with self-reported and objectively determined cardiometabolic risk factors SO SLEEP MEDICINE LA English DT Article DE Sleep duration; Epidemiology; Obesity; Cardiovascular disease; Hypertension; Cholesterol; Diabetes ID HEALTH INTERVIEW SURVEY; CARDIOVASCULAR-DISEASE; UNITED-STATES; LONG-SLEEP; NATIONAL-HEALTH; INSULIN-RESISTANCE; BLOOD-PRESSURE; METABOLIC CONSEQUENCES; HYPERTENSION INCIDENCE; INFLAMMATORY MARKERS AB Background: Self-reported short or long sleep duration has been associated with adverse cardiometabolic health outcomes in laboratory and epidemiologic studies, but interpretation of such data has been limited by methodologic issues. Methods: Adult respondents of the 2007-2008 US National Health and Nutrition Examination Survey (NHANES) were examined in a cross-sectional analysis (N = 5649). Self-reported sleep duration was categorized as very short (< 5 h), short (5-6 h), normal (7-8 h), or long (>= 9 h). Obesity, diabetes mellitus (DM), hypertension, and hyperlipidemia were objectively assessed by self-reported history. Statistical analyses included univariate comparisons across sleep duration categories for all variables. Binary logistic regression analyses and cardiometabolic factor as outcome, with sleep duration category as predictor, were assessed with and without covariates. Observed relationships were further assessed for dependence on race/ethnicity. Results: In adjusted analyses, very short sleep was associated with self-reported hypertension (odds ratio [OR], 2.02, [95% confidence interval {CI}, 1.45-2.81]; P < 0.0001), self-reported hyperlipidemia (OR, 1.96 [95% CI, 1.43-2.69]; P < 0.0001), objective hyperlipidemia (OR, 1.41 [95% CI, 1.04-1.91]; P = 0.03), self-reported DM (OR, 1.76 [95% CI, 1.13-2.74]; P = 0.01), and objective obesity (OR, 1.53 [95% CI, 1.03-1.43]; P = 0.005). Regarding short sleep (5-6 h), in adjusted analyses, elevated risk was seen for self-reported hypertension (OR, 1.22 [95% CI, 1.02-1.45]; P = 0.03) self-reported obesity (OR, 1.21 [95% CI, 1.03-1.43]; P = 0.02), and objective obesity (OR, 1.17 [95% CI, 1.00-1.38]; P < 0.05). Regarding long sleep (>= 9 h), no elevated risk was found for any outcomes. Interactions with race/ethnicity were significant for all outcomes; race/ethnicity differences in patterns of risk varied by outcome studied. In particular, the relationship between very short sleep and obesity was strongest among blacks and the relationship between short sleep and hypertension is strongest among non-Hispanic whites, blacks, and non-Mexican Hispanics/Latinos. Conclusions: Short sleep duration is associated with self-reported and objectively determined adverse cardiometabolic outcomes, even after adjustment for many covariates. Also, these patterns of risk depend on race/ethnicity. (C) 2013 Elsevier B. V. All rights reserved. C1 [Grandner, Michael A.; Chakravorty, Subhajit; Perlis, Michael L.; Oliver, Linden] Univ Penn, Perelman Sch Med, Dept Psychiat, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Grandner, Michael A.; Chakravorty, Subhajit; Perlis, Michael L.; Gurubhagavatula, Indira] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Chakravorty, Subhajit; Gurubhagavatula, Indira] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Gurubhagavatula, Indira] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Grandner, MA (reprint author), Univ Penn, Ctr Sleep & Circadian Neurobiol, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM grandner@upenn.edu FU NCRR NIH HHS [UL1 RR024134]; NHLBI NIH HHS [K23 HL110216]; NIEHS NIH HHS [R21 ES022931] NR 128 TC 52 Z9 53 U1 4 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD JAN PY 2014 VL 15 IS 1 BP 42 EP 50 DI 10.1016/j.sleep.2013.09.012 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 283BW UT WOS:000329220600008 PM 24333222 ER PT J AU Brent, GA AF Brent, Gregory A. TI Commentary on: "American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models," Bianco et al. SO THYROID LA English DT Editorial Material ID THERMOGENESIS; MUTATION C1 [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu NR 10 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2014 VL 24 IS 1 BP 1 EP 2 DI 10.1089/thy.2013.0679 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 285YM UT WOS:000329431000001 PM 24303889 ER PT J AU Ross, DS Tuttle, RM AF Ross, Douglas S. Tuttle, R. Michael TI Observing Micopapillary Thyroid Cancers SO THYROID LA English DT Editorial Material ID OCCULT PAPILLARY CARCINOMA; PLACEBO-CONTROLLED TRIAL; LYMPH-NODE METASTASIS; SUPPRESSIVE THERAPY; NECK DISSECTION; NODULAR GOITER; AUTOPSY; MICROCARCINOMA; LEVOTHYROXINE; METAANALYSIS C1 [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid WAC 730,15 Parkman St, Boston, MA 02114 USA. EM dross@partners.org NR 37 TC 8 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2014 VL 24 IS 1 BP 3 EP 6 DI 10.1089/thy.2013.0659 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 285YM UT WOS:000329431000002 PM 24404786 ER PT J AU McLeod, DSA Cooper, DS Ladenson, PW Ain, KB Brierley, JD Fein, HG Haugen, BR Jonklaas, J Magner, J Ross, DS Skarulis, MC Steward, DL Maxon, HR Sherman, SI AF McLeod, Donald S. A. Cooper, David S. Ladenson, Paul W. Ain, Kenneth B. Brierley, James D. Fein, Henry G. Haugen, Bryan R. Jonklaas, Jacqueline Magner, James Ross, Douglas S. Skarulis, Monica C. Steward, David L. Maxon, Harry R. Sherman, Steven I. CA Natl Thyroid Canc Treatment Cooper TI Prognosis of Differentiated Thyroid Cancer in Relation to Serum Thyrotropin and Thyroglobulin Antibody Status at Time of Diagnosis SO THYROID LA English DT Article ID CHRONIC LYMPHOCYTIC THYROIDITIS; STAGING SYSTEMS; PAPILLARY; CARCINOMA; RISK; DISEASE; TSH; SUPPRESSION; PROGRESSION; RECURRENCE AB Background: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis. Objective: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry. Methods: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) or perioperative TgAb status (n=1770; the TgAb cohort) were analyzed for tumor stage, persistent disease, recurrence, and overall survival (OS; median follow-up, 5.5 years). Parametric tests assessed log-transformed TSH, and categorical variables were tested with chi square. Disease-free survival (DFS) and OS was assessed with Cox models. Results: Geometric mean serum TSH levels were higher in patients with higher-stage disease (Stage III/IV=1.48 vs. 1.02mU/L for Stages I/II; p=0.006). The relationship persisted in those aged 45 years after adjusting for sex (p=0.01). Gross extrathyroidal extension (p=0.03) and presence of cervical lymph node metastases (p=0.003) were also significantly associated with higher serum TSH. Disease recurrence and all-cause mortality occurred in 37 and 38 TSH cohort patients respectively, which limited the power for survival analysis. Positive TgAb was associated with lower stage on univariate analysis (positive TgAb in 23.4% vs. 17.8% of Stage I/II vs. III/IV patients, respectively; p=0.01), although the relationship lost significance when adjusting for age and sex (p=0.34). Perioperative TgAb was not an independent predictor of DFS (hazard ratio=1.12 [95% confidence interval=0.74-1.69]) or OS (hazard ratio=0.98 [95% confidence interval=0.56-1.72]). Conclusions: Preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases. Perioperative TgAb is not an independent predictor of DTC prognosis. A larger cohort is required to assess whether preoperative serum TSH level predicts recurrence or mortality. C1 [McLeod, Donald S. A.] Royal Brisbane & Womens Hosp, Dept Internal Med & Aged Care, Herston, Qld 4029, Australia. [McLeod, Donald S. A.] Royal Brisbane & Womens Hosp, Dept Endocrinol, Herston, Qld 4029, Australia. [McLeod, Donald S. A.] Queensland Inst Med Res, Canc Control Grp, Herston, Qld 4006, Australia. [Cooper, David S.; Ladenson, Paul W.] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD USA. [Ain, Kenneth B.] Vet Affairs Med Ctr, Dept Internal Med, Lexington, KY USA. [Ain, Kenneth B.] Univ Kentucky, Lexington, KY USA. [Brierley, James D.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. [Fein, Henry G.] Sinai Hosp, Div Endocrinol & Metab, Baltimore, MD 21215 USA. [Haugen, Bryan R.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USA. [Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol, Washington, DC 20007 USA. [Magner, James] Genzyme Corp, Cambridge, MA USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Skarulis, Monica C.] NIH, Diabet Endocrinol Obes Branch, Bethesda, MD 20892 USA. [Steward, David L.] Univ Cincinnati, Med Ctr, Dept Head & Neck Surg, Cincinnati, OH 45267 USA. [Maxon, Harry R.] Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45267 USA. [Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. RP McLeod, DSA (reprint author), Royal Brisbane & Womens Hosp, Dept Internal Med & Aged Care, Herston, Qld 4029, Australia. EM donald.mcleod@qimr.edu.au RI Jonklaas, Jacqueline/G-2807-2010; McLeod, Donald/C-4242-2014; OI Jonklaas, Jacqueline/0000-0002-2238-2666; McLeod, Donald/0000-0003-1131-020X; Sherman, Steven/0000-0002-3079-5153 FU Genzyme Corporation; Pfizer; University of Texas M.D. Anderson Cancer Center Support Grant (NCI Grant) [P30 CA016672]; Royal Australasian College of Physicians IMS Traveling Fellowship; Cancer Council Queensland PhD scholarship FX The NTCTCSG is supported in part by research grants from Genzyme Corporation and Pfizer, and by the University of Texas M.D. Anderson Cancer Center Support Grant (NCI Grant P30 CA016672). A Royal Australasian College of Physicians IMS Traveling Fellowship and a Cancer Council Queensland PhD scholarship supported D. S. A. M. We, as principal investigators at each NTCTCSG institution, thank the physicians and staff members who participated in the management and follow-up of these patients. We acknowledge the substantial contributions of the institutional research staff that collected and submitted the data, including Shehnaz Bana, Marge E. Ewertz, RN, and Beverly McLaughlin, RMA. We also appreciate the considerable assistance provided by Jeffrey Cui for the management of NTCTCSG's databases. Finally, we acknowledge the efforts of the numerous physicians and scientists whose contributions were critical in the early years of the registry. NR 37 TC 25 Z9 25 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2014 VL 24 IS 1 BP 35 EP 42 DI 10.1089/thy.2013.0062 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 285YM UT WOS:000329431000006 PM 23731273 ER PT J AU McKee, AC Daneshvar, DH Alvarez, VE Stein, TD AF McKee, Ann C. Daneshvar, Daniel H. Alvarez, Victor E. Stein, Thor D. TI The neuropathology of sport SO ACTA NEUROPATHOLOGICA LA English DT Review ID TRAUMATIC BRAIN-INJURY; PROFESSIONAL FOOTBALL PLAYERS; REPETITIVE HEAD-INJURY; HIGH-SCHOOL FOOTBALL; MILD COGNITIVE IMPAIRMENT; AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID PRECURSOR PROTEIN; RETIRED NFL PLAYERS; STATES HIGH-SCHOOL; PHYSICAL-ACTIVITY AB The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional wrestling, soccer, rugby, and baseball. C1 [McKee, Ann C.; Stein, Thor D.] VA Boston HealthCare Syst, Boston, MA 02130 USA. [McKee, Ann C.; Stein, Thor D.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [McKee, Ann C.; Daneshvar, Daniel H.; Alvarez, Victor E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.] Boston Univ, Sch Med, Alzheimer Dis Ctr, Boston, MA 02118 USA. [McKee, Ann C.; Daneshvar, Daniel H.; Alvarez, Victor E.; Stein, Thor D.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. RP McKee, AC (reprint author), VA Boston HealthCare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM ann.mckee@va.gov OI Daneshvar, Daniel/0000-0003-3691-9513; Stein, Thor/0000-0001-6954-4477 FU Department of Veterans Affairs; Veterans Affairs Biorepository [CSP 501]; Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS); Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; Sports Legacy Institute; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846, 0572063345-5]; National Institute of Aging Boston University Framingham Heart Study [AG1649]; National Operating Committee on Standards for Athletic Equipment; National Football League; Andlinger Foundation; Worldwide Wrestling Entertainment FX We gratefully acknowledge the extraordinary help of Christopher Nowinski, Lisa McHale, Dr. Robert Stern, Dr. Robert Cantu, and all other members of the Center for the Study of Traumatic Encephalopathy at Boston University and Boston VA, as well as the individuals and families whose participation and contributions made this work possible. We also gratefully acknowledge the use of resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA) and Dr. Peter Davies for antibodies. This work was supported by the Department of Veterans Affairs; Veterans Affairs Biorepository (CSP 501); Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS); Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C); Sports Legacy Institute; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846; supplement 0572063345-5; National Institute of Aging Boston University Framingham Heart Study R01 [AG1649]; National Operating Committee on Standards for Athletic Equipment. This work was also supported by unrestricted gifts from the National Football League, the Andlinger Foundation, and Worldwide Wrestling Entertainment. NR 200 TC 73 Z9 74 U1 32 U2 130 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2014 VL 127 IS 1 BP 29 EP 51 DI 10.1007/s00401-013-1230-6 PG 23 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 283DL UT WOS:000329225300003 PM 24366527 ER PT J AU Gotto, AM Cannon, CP Li, XS Vaidya, S Kher, U Brinton, EA Davidson, M Moon, JE Shah, S Dansky, HM Mitchel, Y Barter, P AF Gotto, Antonio M., Jr. Cannon, Christopher P. Li, Xiujiang Susie Vaidya, Sanskruti Kher, Uma Brinton, Eliot A. Davidson, Michael Moon, Jennifer E. Shah, Sukrut Dansky, Hayes M. Mitchel, Yale Barter, Philip CA DEFINE Investigators TI Evaluation of Lipids, Drug Concentration, and Safety Parameters Following Cessation of Treatment With the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib in Patients With or at High Risk for Coronary Heart Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LDL CHOLESTEROL; CETP INHIBITOR; EFFICACY; DYSLIPIDEMIA AB The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer protein inhibitor anacetrapib was previously shown to reduce low-density lipoprotein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoprotein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placebo-adjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoprotein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n = 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing. (C) 2014 Elsevier Inc. All rights reserved. C1 [Gotto, Antonio M., Jr.; Moon, Jennifer E.] Weill Cornell Med Coll, Off Vice President, New York, NY USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Li, Xiujiang Susie; Vaidya, Sanskruti; Kher, Uma; Shah, Sukrut; Dansky, Hayes M.; Mitchel, Yale] Merck Res Labs, Rahway, NJ USA. [Brinton, Eliot A.] Utah Fdn Biomed Res, Salt Lake City, UT USA. [Brinton, Eliot A.] Utah Lipid Ctr, Salt Lake City, UT USA. [Davidson, Michael] Radiant Res, Chicago, IL USA. [Barter, Philip] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. RP Gotto, AM (reprint author), Weill Cornell Med Coll, Off Vice President, New York, NY USA. EM amg2004@med.cornell.edu FU Merck Research Laboratories, Rahway, New Jersey FX This study was funded by Merck Research Laboratories, Rahway, New Jersey. NR 11 TC 37 Z9 37 U1 0 U2 19 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2014 VL 113 IS 1 BP 76 EP 83 DI 10.1016/j.amjcard.2013.08.041 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 284QA UT WOS:000329333800014 PM 24188894 ER PT J AU Velagaleti, RS Gona, P Pencina, MJ Aragam, J Wang, TJ Levy, D D'Agostino, RB Lee, DS Kannel, WB Benjamin, EJ Vasan, RS AF Velagaleti, Raghava S. Gona, Philimon Pencina, Michael J. Aragam, Jayashri Wang, Thomas J. Levy, Daniel D'Agostino, Ralph B. Lee, Douglas S. Kannel, William B. Benjamin, Eme Lia J. Vasan, Ramachandran S. TI Left Ventricular Hypertrophy Patterns and Incidence of Heart Failure With Preserved Versus Reduced Ejection Fraction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; LONGITUDINAL TRACKING; CARDIOVASCULAR HEALTH; HYPERTENSIVE PATIENTS; GEOMETRIC PATTERNS; WALL STRESS; FRAMINGHAM; MASS; DISEASE AB Higher left ventricular (LV) mass, wall thickness, and internal dimension are associated with increased heart failure (HF) risk. Whether different LV hypertrophy patterns vary with respect to rates and types of HF incidence is unclear. In this study, 4,768 Framingham Heart Study participants (mean age 50 years, 56% women) were classified into 4 mutually exclusive LV hypertrophy pattern groups (normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy) using American Society of Echocardiography recommended thresholds of echocardiographic LV mass indexed to body surface area and relative wall thickness, and these groups were related to HF incidence. Whether risk for HF types (HF with reduced ejection fraction [<45%] vs preserved ejection fraction [>= 45%]) varied by hypertrophy pattern was then evaluated. On follow-up (mean 21 years), 458 participants (9.6%, 250 women) developed new-onset HF. The age- and gender-adjusted 20-year HF incidence increased from 6.96% in the normal left ventricle group to 8.67%, 13.38%, and 15.27% in the concentric remodeling, concentric hypertrophy, and eccentric hypertrophy groups, respectively. After adjustment for co-morbidities and incident myocardial infarction, LV hypertrophy patterns were associated with higher HF incidence relative to the normal left ventricle group (p = 0.0002); eccentric hypertrophy carried the greatest risk (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.41 to 2.54), followed by concentric hypertrophy (HR 1.40, 95% CI 1.04 to 1.87). Participants with eccentric hypertrophy had a higher propensity for HF with reduced ejection fraction (HR 2.23, 95% CI 1.48 to 3.37), whereas those with concentric hypertrophy were more prone to HF with preserved ejection fraction (HR 1.66, 95% CI 1.09 to 2.51). In conclusion, in this large community-based sample, HF risk varied by LV hypertrophy pattern, with eccentric and concentric hypertrophy predisposing to HF with reduced and preserved ejection fraction, respectively. (C) 2014 Elsevier Inc. All rights reserved. C1 [Velagaleti, Raghava S.; Gona, Philimon; Pencina, Michael J.; Levy, Daniel; D'Agostino, Ralph B.; Kannel, William B.; Benjamin, Eme Lia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Velagaleti, Raghava S.] Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA USA. [Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Aragam, Jayashri] Vet Adm Hosp, West Roxbury, MA USA. [Aragam, Jayashri; Wang, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. [Benjamin, Eme Lia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Eme Lia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM vasan@bu.edu RI Lee, Douglas/J-4315-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-25195]; National Institutes of Health, Bethesda, Maryland [RO1 HL67288] FX This work was supported by the Contract N01-HC-25195 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland, and Grant RO1 HL67288 from the National Institutes of Health, Bethesda, Maryland. NR 30 TC 25 Z9 25 U1 0 U2 8 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2014 VL 113 IS 1 BP 117 EP 122 DI 10.1016/j.amjcard.2013.09.028 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 284QA UT WOS:000329333800020 PM 24210333 ER PT J AU Roseman, DA Hwang, SJ Manders, ES O'Donnell, CJ Upadhyay, A Hoffmann, U Fox, CS AF Roseman, Daniel A. Hwang, Shih-Jen Manders, Emily S. O'Donnell, Christopher J. Upadhyay, Ashish Hoffmann, Udo Fox, Caroline S. TI Renal Artery Calcium, Cardiovascular Risk Factors, and Indexes of Renal Function SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ANGIOTENSIN-ALDOSTERONE SYSTEM; VASCULAR CALCIFICATIONS; COMPUTED-TOMOGRAPHY; KIDNEY-DISEASE; MICROALBUMINURIA; FRAMINGHAM; STIFFNESS; ATHEROSCLEROSIS; RACE; MEN AB Vascular calcium is well studied in the coronary and peripheral arteries, although there are limited data focusing on calcium deposits specific to renal arteries. The associations among renal artery calcium (RAC), cardiovascular disease risk factors, and indexes of renal function are unknown. We examined 2,699 Framingham Heart Study participants who were part of a multidetector computed tomography substudy from 2008 to 2011. RAC was measured as a calcified plaque of >130 HU and an area of >3 contiguous pixels. Detectable RAC was defined as an Agatston score >0. Chronic kidney disease was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Microalbuminuria was defined as an albumin/creatinine ratio of >= 17 mg/g for men and >= 25 mg/g for women. Multivariable adjusted logistic regression models were used to evaluate the associations between RAC, cardiovascular disease risk factors, and renal function. The associations were secondarily adjusted for coronary artery calcium (CAC) that was used as a marker of nonrenal systemic vascular calcium. The prevalence of RAC was 28.2%; this was similar in women (28.8%) and men (27.5%). Patients with RAC had a higher odds of microalbuminuria (Odds ratio [OR] 1.79, 95% confidence interval [CI] 1.22 to 2.61, p = 0.003), hypertension (OR 2.11, 95% CI 1.69 to 2.64, p<0.001), and diabetes (OR 1.60, 95% CI 1.14 to 2.24, p = 0.01) but not chronic kidney disease (OR 0.87, 95% CI 0.58 to 1.32). After adjustment for CAC, the association with microalbuminuria and hypertension persisted, but the association with diabetes became nonsignificant. In conclusion, RAC is common and independently associated with microalbuminuria and hypertension after adjustment for nonrenal vascular calcium. RAC may be uniquely associated with these markers of renal end-organ damage. Published by Elsevier Inc. C1 [Roseman, Daniel A.; Upadhyay, Ashish] Boston Univ, Med Ctr, Renal Sect, Boston, MA USA. [Hwang, Shih-Jen; Manders, Emily S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Upadhyay, Ashish/0000-0002-0536-5776 FU Boston University from the National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health (Bethesda, Maryland) [T32-DK-007053] FX The Framingham Heart Study is conducted and supported in collaboration with Boston University by contract N01-HC-25195 from the National Heart, Lung, and Blood Institute; Dr. Roseman received funding from grant T32-DK-007053, National Institutes of Health (Bethesda, Maryland). NR 25 TC 6 Z9 9 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2014 VL 113 IS 1 BP 156 EP 161 DI 10.1016/j.amjcard.2013.09.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 284QA UT WOS:000329333800027 PM 24210678 ER PT J AU Maron, BJ Josephson, ME AF Maron, Barry J. Josephson, Mark E. TI Long-Term Consequences of the Right Ventricular Pacing Mania of the 1990s for Obstructive Hypertrophic Cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID ATRIAL-FIBRILLATION; HEART-FAILURE; DOUBLE-BLIND; CROSSOVER; REDUCTION; THERAPY; IMPACT; TRIAL C1 [Maron, Barry J.] Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA. [Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA. NR 12 TC 2 Z9 2 U1 2 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2014 VL 113 IS 1 BP 191 EP 192 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 284QA UT WOS:000329333800034 PM 24239321 ER PT J AU Camargo, CA Manson, JE AF Camargo, Carlos A., Jr. Manson, JoAnn E. TI Vitamin D supplementation and risk of infectious disease: no easy answers SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID RESPIRATORY-TRACT INFECTIONS; TRIAL C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU NCI NIH HHS [CA-138962, R01 CA138962, U01 CA138962]; NIAID NIH HHS [AI-93723, R01 AI093723] NR 10 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2014 VL 99 IS 1 BP 3 EP 4 DI 10.3945/ajcn.113.078329 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 281DN UT WOS:000329080200002 PM 24284446 ER PT J AU Amparo, F Jin, YP Hamrah, P Schaumberg, DA Dana, R AF Amparo, Francisco Jin, Yiping Hamrah, Pedram Schaumberg, Debra A. Dana, Reza TI What is the Value of Incorporating Tear Osmolarity Measurement in Assessing Patient Response to Therapy in Dry Eye Disease? SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID FILM OSMOLARITY; ELECTRICAL-IMPEDANCE; TESTS; HYPEROSMOLARITY; QUESTIONNAIRE; REPEATABILITY; SYMPTOMS; CORNEAL; INDEX; SIGNS AB PURPOSE: To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED). DESIGN: Retrospective, clinic-based cohort study. METHODS: In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from 2 separate visits. Main outcomes included the correlation of the changes between the 2 visits for tear osmolarity (Tear Lab system), symptoms (Ocular Surface Disease Index), and corneal fluorescein staining (modified Oxford scheme). For teat osmolarity and corneal fluorescein staining the scores from the eye with highest readings were analyzed. The correlations were repeated on subgroups based on proposed cutoffs for DED severity and on patients' treatment. RESULTS: We found a modest, though statistically significant, correlation between changes in. corneal fluorescein staining and symptoms of DED (R = 0.31; P < .001). However, there was no correlation between the recorded change in tear osmolarity and symptoms (R = -0.091; P = .38) or between changes in tear osmolarity and corneal fluorescein staining (R = -0.02; P = .80). This lack of correlation was consistent in all the subgroups studied. A multivariate analysis revealed that changes in corneal fluorescein staining had predictive value on symptom changes, whereas tear osmolarity changes did not. CONCLUSIONS: Changes in tear osmolarity do not correlate significantly with changes in patient symptoms or corneal fluorescein staining in dry eye disease. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Amparo, Francisco; Jin, Yiping; Hamrah, Pedram; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Schaumberg, Debra A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Schaumberg, Debra A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institutes of Health, Bethesda, Maryland [K24 EY019098] FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. RD is consultant to Alcon, Allergan, Bausch and Lomb, Eleven Biotherapeutics, Genentech, Google, Kala, and Novabay. He holds equity at Eleven Biotherapeutics. Supported in part by Grant K24 EY019098 from the National Institutes of Health, Bethesda, Maryland. Contributions of authors: design of study (F.A., RD.); conduct of study (F.A., J.Y., R.D., PE.); collection of data (F.A., J.Y.); management, analysis, and interpretation of data (F.A., J.Y., R.D., D.S., P.H.); preparation and review of manuscript (F.A., J.Y., R.D., D.S., P.H.). The authors thank Leila Smaga. and the members of the Cornea Research Department, Massachusetts Eye & Ear Infirmary, for their invaluable support in study management. NR 29 TC 26 Z9 27 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 2014 VL 157 IS 1 BP 69 EP 77 DI 10.1016/j.ajo.2013.07.019 PG 9 WC Ophthalmology SC Ophthalmology GA 283UR UT WOS:000329273000012 PM 24060433 ER PT J AU Jakobiec, FA Mendoza, PR AF Jakobiec, Frederick A. Mendoza, Pia R. TI Eyelid Sebaceous Carcinoma: Clinicopathologic and Multiparametric Immunohistochemical Analysis That Includes Adipophilin SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MUIR-TORRE SYNDROME; BASAL-CELL; GLAND CARCINOMA; CUTANEOUS HORN; LACRIMAL GLAND; UTERINE CERVIX; OCULAR ADNEXA; DIFFERENTIATION; TUMORS AB PURPOSE: To evaluate the fine cytopathologic features and immunohistochemistry of eyelid sebaceous carcinoma. DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records and microscopic glass slides of 12 patients diagnosed with sebaceous carcinoma were reviewed. Paraffin-embedded tissue recuts were immunoreacted for epithelial membrane antigen (EMA), Ber-EP4, p.53, Ki-67, and adipophilin for cytoplasmic lipid. Invasive growth and intraepithelial spread were analyzed separately. Cytoplasmic and nuclear characteristics were correlated with the results of the immunohistochemical profiling. RESULTS: Five patients experienced recurrences, but no metastases or tumor-related deaths were discovered. The nuclei in 11 invasive tumor cells were typically round with finely divided, granular, or smudgy chromatin without prominent margination at the nuclear membrane; they exhibited small punctate nucleoli. Positivity for EMA (both diffuse and focal), p53 (72% of nuclei), and Ki-67 (45% proliferation index) was demonstrated. Adipophilin positivity in vesicular and granular forms was detected in paraffin sections in all invasive tumors, most prominently in moderately differentiated and well-differentiated lesions. Among 9 cases exhibiting intraepithelial extensions, 6 showed mostly granular positivity and 3 vesicular positivity. p53 identified residual atypical intraepithelial cells when conjunctival epithelial sloughing occurred. CONCLUSIONS: Immunohistochemistry can make significant contributions to the diagnosis of sebaceous carcinoma. p53 and vesicular granular adipophilin positivity were highly reliable in supplementing the routine microscopic diagnosis of infiltrative tumors and both can be used in paraffin sections, thereby obviating cumbersome oil red 0 staining of frozen sections. The cells found in intraepithelial spread were strongly EMA and p53 positive, with more granular than vesicular adipophilin positivity. ((C) 2014 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_jakobiec@meei.harvard.edu NR 88 TC 15 Z9 15 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 2014 VL 157 IS 1 BP 186 EP 208 DI 10.1016/j.ajo.2013.08.015 PG 23 WC Ophthalmology SC Ophthalmology GA 283UR UT WOS:000329273000027 PM 24112633 ER PT J AU Wagner, B Gorin, Y AF Wagner, Brent Gorin, Yves TI Src tyrosine kinase mediates platelet-derived growth factor BB-induced and redox-dependent migration in metanephric mesenchymal cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE mesenchyme; metanephric; migration; Nox4; platelet-derived growth factor ID SMOOTH-MUSCLE-CELLS; FACTOR RECEPTOR-BETA; NADPH OXIDASE 4; SIGNAL-REGULATED KINASE; ANGIOTENSIN-II; PROTEIN-KINASE; MESANGIAL CELLS; ENDOTHELIAL-CELLS; NAD(P)H OXIDASE; DNA-SYNTHESIS AB The adult kidney is derived from the interaction between the metanephric blastema and the ureteric bud. Platelet-derived growth factor (PDGF) receptor beta is essential for the development of the mature glomerular tuft, as mice deficient for this receptor lack mesangial cells. This study investigated the role of Src tyrosine kinase in PDGF-mediated reactive oxygen species (ROS) generation and migration of metanephric mesenchymal cells (MMCs). Cultured embryonic MMCs from wildtype and PDGF receptor-deficient embryos were established. Migration was determined via wound-healing assay. Unlike PDGF AA, PDGF BB-induced greater migration in MMCs with respect to control. This was abrogated by neutralizing an antibody to PDGF BB. Phosphatidylinositol 3-kinase (PI3K) inhibitors suppressed PDGF BB-induced migration. Conversely, mitogen-activated protein kinase/ extracellular signal-regulated kinase (MEK) inhibitors had no effect. Src inhibitors inhibited PDGF-induced cell migration, PI3K activity, and Akt phosphorylation. Adenoviral dominant negative Src (AD DN Src) abrogated PDGF BB-induced Akt phosphorylation. Hydrogen peroxide stimulated cell migration. PDGF BB-induced wound closure was inhibited by the antioxidants N-acetyl-L-cysteine, tiron, and the flavoprotein inhibitor diphenyleneiodonium. These cells express the NADPH oxidase homolog Nox4. Inhibiting Nox4 with antisense oligonucleotides or small interfering RNA (siRNA) suppressed PDGF-induced wound closure. Inhibition of Src with siRNA reduced PDGF BB-induced ROS generation as assessed by 2', 7'-dichlorodihydrofluorescein diacetate fluorescence. Furthermore, PDGF BB-stimulated ROS generation and migration were similarly suppressed by Ad DN Src. In MMCs, PDGF BB-induced migration is mediated by PI3K and Src in a redoxdependent manner involving Nox4. Src may be upstream to PI3K and Nox4. C1 [Wagner, Brent] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Wagner, Brent; Gorin, Yves] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. RP Wagner, B (reprint author), South Texas Vet Hlth Care Syst, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wagnerb@uthscsa.edu OI Wagner, Brent/0000-0002-7063-0142 FU American Heart Association [121052]; Department of Veterans Affairs Career Development Award; Department of Veterans Affairs Merit Award; Juvenile Diabetes Research Foundation Grant; National Institute of Diabetes and Digestive and Kidney Diseases [DK-079996] FX This work was supported by a Fellow-to-Faculty Transition Award from the American Heart Association (no. 121052). B. Wagner is supported by a Department of Veterans Affairs Career Development Award and a Department of Veterans Affairs Merit Award. Y. Gorin is supported by a Juvenile Diabetes Research Foundation Grant and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-079996. NR 91 TC 2 Z9 2 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2014 VL 306 IS 1 BP F85 EP F97 DI 10.1152/ajprenal.00371.2013 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 282SL UT WOS:000329193300011 PM 24197068 ER PT J AU Pollack, MH Van Ameringen, M Simon, NM Worthington, JW Hoge, EA Keshaviah, A Stein, MB AF Pollack, Mark H. Van Ameringen, Michael Simon, Naomi M. Worthington, John W. Hoge, Elizabeth A. Keshaviah, Aparna Stein, Murray B. TI A Double-Blind Randomized Controlled Trial of Augmentation and Switch Strategies for Refractory Social Anxiety Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHOMETRIC PROPERTIES; PHOBIA; PLACEBO; SCALE; PAROXETINE; THERAPY AB Objective: Most patients remain symptomatic after an initial intervention with approved treatments for generalized social anxiety disorder. This randomized controlled trial provides systematic, prospectively derived data on the relative benefits of "next-step" pharmacotherapies to improve outcomes for individuals with generalized social anxiety disorder who remain symptomatic after initial treatment. Method: This three site, 12-week; double-blind randomized controlled trial compared the relative benefits of three strategies for patients remaining symptomatic (Liebowiiz Social Anxiety Scale [LSAS] score >50) after a 10-week trial of seriraline alone: the addition of up to 3.0 mg/day of clonazepam (sertraline plus clonazepam), a switch to up to 225 mg/day of venlafaxine, or prolonged sertraline treatment with placebo (sertraline plus placebo). Results: A total of 397 participants received at least one dose of sertraline; 181 nonresponders (LSAS score >50) at week 10 were randomly assigned to sertraline plus clonazepam, switch to venlafaxine, or sertraline plus placebo, Overall, 21% of patients achieved remission (LSAS score <= 30) at the endpoint, and 27% of patients assigned to sertraline plus clonazepam achieved remission compared with patients assigned to sertraline plus placebo (17%) or venlafaxine (19%), but the differences did not reach significance. Sertraline plus clonazepam was associated with a significantly greater drop in LSAS severity (p=0.020) and disability (p=0.0028) compared with sertraline plus placebo; no significant differences were observed on these parameters between venlafaxine and either sertraline plus placebo or sertraline plus clonazepam. In supplemental analysis, the overall response rate (LSAS score <= 50) was 46%, including a significantly greater proportion of patients in the sertraline plus clonazepam group (56%) compared with the sertraline plus placebo group responding (36%; p=0.027); differences did not reach significance between venlafaxine and sertraline plus placebo or sertraline plus clonazepam. Conclusions: The findings suggest that the clonazepam augmentation strategy provides relative benefits for sertraline nonresponders in social anxiety disorder. C1 [Pollack, Mark H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. McMaster Univ, Hamilton, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Pollack, MH (reprint author), Rush Univ, Med Ctr, Chicago, IL 60612 USA. EM mark_pollack@rush.edu RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 FU NIMH [1R01MH070919]; Brain Cells; Concept Pharma; Corcept; Edgemont; Eli Lilly; Ironwood Pharmaceuticals; Johnson and Johnson; Labopharm; Medavante; Merck; Mindsite; Otsuka; Pfizer; Sepracor; Targia; Transcept; Bristol-Myers Squibb; Euthymics; Forest Laboratories; GlaxoSmithKline; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; NIMH; AstraZeneca; Structured Interview Guide for the Hamilton Anxiety Scale; SAFER interviews; Canadian Foundation for Innovation; Janssen-Ortho; NIH; Wyeth-Ayerst; Biovail; American Cancer Society; American Foundation for Suicide Prevention; Department of Defense; Highland Street Foundation; Massachusetts General Hospital Psychiatry Academy; NARSAD FX Supported by NIMH (grant 1R01MH070919). Support for study drug and packaging received from Pfizer and Wyeth Pharmaceuticals.; Dr. Pollack has received advisory board or consulting fees from Brain Cells, Concept Pharma, Corcept, Edgemont, Eli Lilly, Ironwood Pharmaceuticals, Johnson and Johnson, Labopharm, Medavante, Merck, Mindsite, Otsuka, Pfizer, Sepracor, Targia, and Transcept; grant support from Bristol-Myers Squibb, Eli Lilly, Euthymics, Forest Laboratories, GlaxoSmithKline, the National Center for Complementary and Alternative Medicine, National Institute on Drug Abuse, NIMH, and Sepracor; CME activity support from AstraZeneca, Pfizer, and Sepracor; royalty or patent funds from the Structured Interview Guide for the Hamilton Anxiety Scale, SAFER interviews; and equity from Doyen Medical, Medavante, Mensante Corporation, Mindsite, and Targia. Dr. Van Ameringen has received grant or research support from the Canadian Foundation for Innovation, Forest Laboratories, Janssen-Ortho, NIH, Pfizer, Servier, and Wyeth-Ayerst and has received speakers bureau, consultant, or advisory board fees from AstraZeneca, Biovail, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen-Ortho, Labo Pharm, Lundbeck, Pfizer, Shire, and Valiant. Dr. Simon has received grant support or consulting fees from the American Cancer Society, American Foundation for Suicide Prevention, Department of Defense, Eli Lilly, Forest Research, GlaxoSmithKline, Highland Street Foundation, Massachusetts General Hospital Psychiatry Academy, NARSAD, NIH, NIMH, Pfizer, and Sepracor and her spouse has equity in Elan, Dandreon, G Zero, and, Gatekeeper. Dr. Worthington has received grant or research support from Eli Lilly, Forest Pharmaceuticals, Pfizer, and Sepracor. Dr. Stein has a patent on the use of genetic testing to predict treatment outcomes in social anxiety disorder and receives payment for his work as Co-Editor-in-Chief of UpToDate in Psychiatry and as Deputy Editor of Depression and Anxiety and Biological Psychiatry. Dr. Hoge and Ms. Keshaviah report no financial relationships with commercial interests. NR 21 TC 18 Z9 19 U1 4 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2014 VL 171 IS 1 BP 44 EP 53 PG 10 WC Psychiatry SC Psychiatry GA 286OO UT WOS:000329478800011 PM 24399428 ER PT J AU Koenigsberg, HW Denny, BT Fan, J Liu, X Guerreri, S Mayson, SJ Rimsky, L New, AS Goodman, M Siever, LJ AF Koenigsberg, Harold W. Denny, Bryan T. Fan, Jin Liu, Xun Guerreri, Stephanie Mayson, Sarah Jo Rimsky, Liza New, Antonia S. Goodman, Marianne Siever, Larry J. TI The Neural Correlates of Anomalous Habituation to Negative Emotional Pictures in Borderline and Avoidant Personality Disorder Patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; FUNCTIONAL MRI; CONNECTIVITY; INSULA; DYSREGULATION; EXPOSURE; BEHAVIOR; STIMULI; FMRI AB Objective: Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder. Method: During fMRI scanning, borderline patients, healthy subjects, and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeated versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups. Results: Unlike healthy subjects, neither borderline nor avoidant personality disorder patients exhibited increased activity in the dorsal anterior cingulate cortex when viewing repeated Versus novel pictures. This lack of an increase in dorsal anterior cingulate activity was associated with greater affective instability in borderline patients. In addition, borderline and avoidant patients exhibited smaller increases in insula-amygdala functional connectivity than healthy subjects and, unlike healthy subjects, did not show habituation in ratings of the emotional intensity of the images. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate functional connectivity during habituation. Conclusions: Unlike healthy subjects, borderline patients fail to habituate to negative pictures, and they differ from both healthy subjects and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline patients. C1 [Koenigsberg, Harold W.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, Bronx, NY USA. CUNY, Queens Coll, Dept Psychol, New York, NY 10021 USA. Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. RP Koenigsberg, HW (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM hwarrenk@nyc.rr.com RI Fan, Jin/A-6716-2009; Liu, Xun/C-2400-2009 OI Fan, Jin/0000-0001-9630-8330; Liu, Xun/0000-0003-1366-8926 FU NIMH [R01 MH077813]; National Center for Research Resources, NIH [5M01 RR00071]; James J. Peters VA Medical Center FX Supported by NIMH grant R01 MH077813 to Dr. Koenigsberg; by the National Center for Research Resources, NIH, for the Mount Sinai General Clinical Research Center (5M01 RR00071); and by the James J. Peters VA Medical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIMH, NIH, or the U.S. Department of Veterans Affairs. NR 38 TC 19 Z9 19 U1 2 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2014 VL 171 IS 1 BP 82 EP 90 DI 10.1176/appi.ajp.2013.13070852 PG 9 WC Psychiatry SC Psychiatry GA 286OO UT WOS:000329478800015 PM 24275960 ER PT J AU Greenberg, D AF Greenberg, Donna TI Psycho-Oncology SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Book Review C1 [Greenberg, Donna] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Greenberg, Donna] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenberg, Donna] Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, D (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2014 VL 171 IS 1 BP 123 EP 124 DI 10.1176/appi.ajp.2013.13081098 PG 2 WC Psychiatry SC Psychiatry GA 286OO UT WOS:000329478800027 ER PT J AU Martinelli, R Kamei, M Sage, PT Massol, R Varghese, L Sciuto, T Toporsian, M Dvorak, AM Kirchhausen, T Springer, TA Carman, CV AF Martinelli, Roberta Kamei, Masataka Sage, Peter T. Massol, Ramiro Varghese, Laya Sciuto, Tracey Toporsian, Mourad Dvorak, Ann M. Kirchhausen, Tomas Springer, Timothy A. Carman, Christopher, V TI Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Martinelli, Roberta; Sage, Peter T.; Varghese, Laya; Sciuto, Tracey; Toporsian, Mourad; Dvorak, Ann M.; Kirchhausen, Tomas; Springer, Timothy A.; Carman, Christopher, V] Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. [Kamei, Masataka] Natl Cerebral & Cardiovasc Ctr, Osaka, Japan. [Massol, Ramiro] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 EI 1573-7209 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2014 VL 17 IS 1 BP 281 EP 282 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 283EJ UT WOS:000329228000046 ER PT J AU Martinelli, R Zeiger, AS Withfield, M Van Vliet, KJ Greenwood, J Carman, CV AF Martinelli, Roberta Zeiger, Adam S. Withfield, Matthew Van Vliet, Krystyn J. Greenwood, John Carman, Christopher, V TI Cellular and biomechanical determinants of leukocyte diapedesis migration route SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Martinelli, Roberta; Carman, Christopher, V] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Zeiger, Adam S.; Withfield, Matthew; Van Vliet, Krystyn J.] MIT, Cambridge, MA 02139 USA. [Greenwood, John] UCL, Inst Ophthalmol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 EI 1573-7209 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2014 VL 17 IS 1 BP 299 EP 299 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 283EJ UT WOS:000329228000110 ER PT J AU Ebrahimi, R Bakaeen, FG Uberoi, A Ardehali, A Baltz, JH Hattler, B Almassi, GH Wagner, TH Collins, JF Grover, FL Shroyer, AL AF Ebrahimi, Ramin Bakaeen, Faisal G. Uberoi, Abhimanyu Ardehali, Abbas Baltz, Janet H. Hattler, Brack Almassi, G. Hossein Wagner, Todd H. Collins, Joseph F. Grover, Frederick L. Shroyer, A. Laurie TI Effect of Clopidogrel Use Post Coronary Artery Bypass Surgery on Graft Patency SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-30, 2013 CL Los Angeles, CA SP Soc Thorac Surg ID ASPIRIN PLUS CLOPIDOGREL; INTERNAL MAMMARY ARTERY; EVENTS CURE TRIAL; SAPHENOUS-VEIN; ANTIPLATELET THERAPY; PLATELET INHIBITION; UNSTABLE ANGINA; ON-PUMP; PREVENTION; OUTCOMES AB Background. Clopidogrel use post coronary artery bypass grafting (CABG) has become more popular under the assumption that it improves graft patency. The purpose of this sub-analysis from the Randomized On and Off-Pump Bypass (ROOBY) trial is to evaluate the role of clopidogrel use post CABG to improve graft patency when added to standard aspirin therapy. Methods. The ROOBY trial was a multi-center, randomized, controlled clinical trial that compared on-pump versus off-pump coronary artery bypass grafting (CABG). Clopidogrel use post CABG was left at the discretion of the operator. Detailed data regarding the use and timing of clopidogrel post CABG were collected prospectively, along with 1-year angiograms to evaluate graft status. Results. Of the 2,203 subjects undergoing CABG, 953 patient records had complete clopidogrel use and 1-year angiographic data. Of these, 345 (36.2%) received clopidogrel post CABG prior to discharge. Compared with patients with no post-CABG clopidogrel use, baseline characteristics were similar for the clopidogrel group except for the following: lower preoperative aspirin use (80.2% vs 86.7%, p = 0.009); higher preoperative clopidogrel use (23.5% vs 14.0%, p < 0.001), less on-pump (35.9% vs 55.9%, p < 0.0001); and lower endoscopic vein harvesting (30.8% vs 42.5%, p < 0.001) rates. Overall 1-year graft patency rates were not different between the clopidogrel and no-clopidogrel groups (86.5% vs 85.3%, p = 0.43). Multivariable analyses did not alter these findings. Conclusions. This study suggests that routine post-CABG clopidogrel use may not translate to improved 1-year graft patency. Future studies appear warranted to better define the role of more aggressive antiplatelet therapy post CABG on graft patency and clinical outcomes. (C) 2014 by The Society of Thoracic Surgeons C1 Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Cardiothorac Surg, Houston, TX 77030 USA. Northport VA Med Ctr, Northport, NY USA. Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. VA Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. VA Palo Alto Hlth Econ Resource Ctr, Menlo Pk, CA USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Zablocki VA Med Ctr, Milwaukee, WI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Ebrahimi, R (reprint author), Greater Los Angeles VA Med Ctr, Dept Med, Cardiol Sect 111E, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ebrahimi@ucla.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 30 TC 14 Z9 16 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2014 VL 97 IS 1 BP 15 EP 21 DI 10.1016/j.athoracsur.2013.08.058 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 282FO UT WOS:000329155900013 PM 24206971 ER PT J AU Mimiaga, MJ Closson, EF Kothary, V Mitty, JA AF Mimiaga, Matthew J. Closson, Elizabeth F. Kothary, Vishesh Mitty, Jennifer A. TI Sexual Partnerships and Considerations for HIV Antiretroviral Pre-Exposure Prophylaxis Utilization Among High-Risk Substance Using Men Who Have Sex with Men SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE Men who have sex with men; Pre-exposure prophylaxis; Sex partners; Substance use; Sexual orientation ID CIRCUIT PARTY ATTENDANCE; CLUB DRUG-USE; BISEXUAL MEN; GAY MEN; MEDICATION ADHERENCE; POSITIVE MEN; US CITIES; MOTIVATIONS; AGREEMENTS; HIV/AIDS AB Men who have sex with men (MSM) remain at great risk of HIV in the United States, representing 65 % of incident HIV infections. One factor contributing to the high rate of HIV infection among MSM is use of "recreational" drugs that are highly associated with unprotected anal sex. Pre-exposure chemoprophylaxis (PrEP) is a novel biomedical HIV prevention strategy that has the potential to reduce HIV transmission in MSM. Main and casual sex partners play a role in HIV prevention efforts for MSM. The study aimed to qualitatively explore the perceived influences of sexual relationships on promoting and inhibiting PrEP use among high-risk MSM who report regular drug use. Semi-structured qualitative interviews were conducted with 40 participants recruited in Boston, Massachusetts. Data were analyzed using descriptive qualitative analysis. Casual partners presented a distinct set of concerns from primary partnerships. MSM generally viewed main partners as a potential source of support for taking PrEP. Given their informal and often temporary nature, PrEP disclosure to casual partners was considered unnecessary. HIV-related stigma and substance use were also perceived as barriers to discussing PrEP use with casual partners. MSM articulated a high degree of personal agency regarding their ability to take PrEP. Findings suggest that behavioral interventions to improve PrEP utilization and adherence for high-risk MSM should be tailored to sex partner type and the parameters established between sex partners. Approaches to PrEP disclosure and partner engagement should be informed by the relative benefits and limitations characterized by these different types of relationships. C1 [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Closson, Elizabeth F.; Kothary, Vishesh; Mitty, Jennifer A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mitty, Jennifer A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Infect Dis, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@partners.org FU NIMH NIH HHS [R21 MH095535, R21 MH085314, R21MH085314-01] NR 29 TC 15 Z9 15 U1 2 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 EI 1573-2800 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD JAN PY 2014 VL 43 IS 1 BP 99 EP 106 DI 10.1007/s10508-013-0208-8 PG 8 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 283HL UT WOS:000329236900013 PM 24243002 ER PT J AU Blashill, AJ Wilson, JM O'Cleirigh, CM Mayer, KH Safren, SA AF Blashill, Aaron J. Wilson, Johannes M. O'Cleirigh, Conall M. Mayer, Kenneth H. Safren, Steven A. TI Examining the Correspondence Between Relationship Identity and Actual Sexual Risk Behavior Among HIV-Positive Men Who Have Sex with Men SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE HIV/AIDS; MSM; Couples; Sexual risk; Monogamy; Sexual orientation ID GAY MALE COUPLES; PREVENTION INTERVENTION; COMMUNITY INTEGRATION; EXTRADYADIC SEX; INFECTED MSM; TRANSMISSION; DEPRESSION; SEROSTATUS; AGREEMENTS; PARTNERS AB Sexual behavior of men who have sex with men (MSM), within and outside of one's primary relationship, may contribute to increased risk of HIV transmission among those living with HIV. The current study sought to understand how HIV-infected MSM report their relationship status and the degree to which this corresponds with their sexual behavior. Further, we examined rates and psychosocial associations with sexual HIV transmission risk behavior (TRB) across relationship categories. In a sample of 503 HIV-infected MSM in HIV care, 200 (39.8 %) reported having a primary partner. Of these, 115 reported that their relationship was open and 85 reported that it was monogamous. Of the 85 who reported a monogamous relationship, 23 (27 %) reported more than one sexual partner in the prior 3 months, 53 (62 %) reported only one partner, and nine did not report on the number of partners in the past 3 months. Hence, there were three categories of relationships: (1) "monogamous with one sexual partner," (2) "monogamous with more than one sexual partner," and (3) "open relationship." The "monogamous with more than one sexual partner" group reported higher TRB and crystal methamphetamine use compared to the "monogamous with one sexual partner" group and different patterns of relationships with TRB emerged across the three groups. Couples-based HIV prevention interventions for MSM may be enhanced by considering that there may be different definitions of monogamy among MSM, and that the context of relationship status may require tailoring interventions to meet the needs of specific subgroups of MSM couples. C1 [Blashill, Aaron J.; Wilson, Johannes M.; O'Cleirigh, Conall M.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.; O'Cleirigh, Conall M.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Blashill, Aaron J.; O'Cleirigh, Conall M.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NIAID NIH HHS [5P30AI060354, P30 AI060354]; NIMH NIH HHS [K24 MH094214, K23MH096647, K23 MH096647, R01 MH068746, K24MH094214, 5R01MH068746-05]; PHS HHS [H97HA01293] NR 29 TC 8 Z9 8 U1 1 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 EI 1573-2800 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD JAN PY 2014 VL 43 IS 1 BP 129 EP 137 DI 10.1007/s10508-013-0209-7 PG 9 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 283HL UT WOS:000329236900016 PM 24198170 ER PT S AU Badr, CE AF Badr, Christian E. BE Badr, CE TI Bioluminescence Imaging: Basics and Practical Limitations SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bioluminescence; Imaging; Photoprotein; Lux; Luciferase ID RENILLA-RENIFORMIS LUCIFERASE; FORKHEAD TRANSCRIPTION FACTOR; REPORTER GENE-EXPRESSION; FIREFLY LUCIFERASE; IN-VIVO; GAUSSIA LUCIFERASE; HIGH-THROUGHPUT; BACTERIAL BIOLUMINESCENCE; SENSITIVE ASSAY; LIVING SUBJECTS AB Over the last three decades, imaging has been a thriving field with continuous egression of more reliable and highly sophisticated tools and techniques allowing better understanding of biological processes in living organisms. This field continues to expand and its applications broaden to encompass limitless applications in various biomedical research areas. It is however, of utmost importance to understand the capabilities and limitations of this technique as new challenges and hurdles continue to arise. This chapter describes the general properties of bioluminescence imaging and commonly used reporters while underlining the challenges and limitations with these modalities. C1 [Badr, Christian E.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Badr, Christian E.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Badr, CE (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. NR 83 TC 9 Z9 10 U1 3 U2 15 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 1 EP 18 DI 10.1007/978-1-62703-718-1_1 D2 10.1007/978-1-62703-718-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700002 PM 24166364 ER PT S AU Badr, CE AF Badr, Christian E. BE Badr, CE TI Bioluminescent Imaging Methods and Protocols Preface SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 [Badr, Christian E.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Badr, Christian E.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Badr, CE (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP V EP V D2 10.1007/978-1-62703-718-1 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700001 ER PT S AU Degeling, MH Bovenberg, MSS Tannous, M Tannous, BA AF Degeling, M. Hannah Bovenberg, M. Sarah S. Tannous, Marie Tannous, Bakhos A. BE Badr, CE TI Gaussia Luciferase-Based Mycoplasma Detection Assay in Mammalian Cell Culture SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mycoplasma contamination; Mycoplasma detection assay; Gluc mycosensor; Cell culture contamination; Antibiotics; Bioluminescence reaction ID IN-VIVO; INFECTION AB Mycoplasma contamination in mammalian cell culture is a common problem with serious consequences on experimental data, and yet many laboratories fail to perform regular testing. In this chapter, we describe a simple and sensitive mycoplasma detection assay based on the bioluminescent properties of the Gaussia luciferase reporter. C1 [Degeling, M. Hannah; Bovenberg, M. Sarah S.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Degeling, M. Hannah; Bovenberg, M. Sarah S.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Bovenberg, M. Sarah S.] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. [Tannous, Marie] Notre Dame Univ, Barsa, Lebanon. RP Degeling, MH (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. FU NINDS NIH HHS [P30NS045776, 1R01NS064983] NR 12 TC 1 Z9 1 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 47 EP 55 DI 10.1007/978-1-62703-718-1_4 D2 10.1007/978-1-62703-718-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700005 PM 24166367 ER PT S AU Amante, RJ Badr, CE AF Amante, Romain J. Badr, Christian E. BE Badr, CE TI Cell-Based Bioluminescence Screening Assays SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Screening; Drugs; Bioluminescence; Gaussia luciferase; Glioblastoma ID GAUSSIA LUCIFERASE; PATHWAY AB Drug screening is an essential and widely used technique for drug discovery in various biomedical fields notably in oncology. Here we describe a functional screening assay based on the bioluminescence detection of a secreted luciferase for monitoring cell viability of cancer cells in a high-throughput format. This assay allows the screening of large libraries comprising thousands of compounds and the identification of potential anticancer molecules in a rapid, facile, and cost-effective manner. C1 [Amante, Romain J.; Badr, Christian E.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Amante, Romain J.; Badr, Christian E.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Amante, RJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 185 EP 195 DI 10.1007/978-1-62703-718-1_15 D2 10.1007/978-1-62703-718-1 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700016 PM 24166378 ER PT S AU Maguire, CA AF Maguire, Casey A. BE Badr, CE TI Bioluminescence-Based Monitoring of Virus Vector-Mediated Gene Transfer in Mice SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE In vivo bioluminescence imaging; Firefly luciferase; Virus vector; Adeno-associated virus (AAV); Optical imaging; Mouse models ID CENTRAL-NERVOUS-SYSTEM; MAMMALIAN-CELLS; LUCIFERASE; ASTROCYTES; NEURONS; TROPISM AB In vivo bioluminescence imaging (BLI) is a powerful technology that gives information on biological processes in living animals over multiple time points. Importantly BLI can also yield anatomical localization of signal which can provide important information when performing biodistribution studies of different macromolecules. This is of particular interest for gene therapy vectors such as adeno-associated virus (AAV)vectors in which knowledge of in vivo gene expression profiles help characterize what target tissues or organs the vector may be useful for. It can also be utilized to assess novel vector systems for their ability to overcome specific in vivo barriers of effective gene therapy. Here we describe BLI of AAV-encoded firefly luciferase (Fluc)expression in mice after intravascular delivery. This protocol can be amended for use with different virus vectors )e.g., lentivirus, adenovirus)as well as nonviral gene delivery )e. g., plasmid DNA, liposomes). C1 [Maguire, Casey A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Maguire, Casey A.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Maguire, CA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU NINDS NIH HHS [1 R21 NS081374-01] NR 13 TC 0 Z9 0 U1 0 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 197 EP 209 DI 10.1007/978-1-62703-718-1_16 D2 10.1007/978-1-62703-718-1 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700017 PM 24166379 ER PT S AU Lewandrowski, GK Magee, CN Mounayar, M Tannous, BA Azzi, J AF Lewandrowski, Grant K. Magee, Ciara N. Mounayar, Marwan Tannous, Bakhos A. Azzi, Jamil BE Badr, CE TI Simultaneous In Vivo Monitoring of Regulatory and Effector T Lymphocytes Using Secreted Gaussia Luciferase, Firefly Luciferase, and Secreted Alkaline Phosphatase SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Luciferase; Bioluminescence imaging; Lymphocytes; Tregs; Homeostasis; Survival; GVHD; Type 1 diabetes ID IMMUNOLOGICAL SELF-TOLERANCE; DYT1 DYSTONIA CELLS; GENE-EXPRESSION; ER STRESS; EX-VIVO; ANTIGEN; PATHWAY; VITRO; INFLAMMATION; INDUCTION AB Regulatory T cells (T regs) are amongst the most widely studied cells in a variety of immune-mediated conditions, including transplantation and Graft Versus Host Disease (GVHD), cancer and autoimmunity; indeed, there is great interest in the tolerogenic potential of T reg -based therapy. Consequently, the need to establish the mechanisms that determine T reg survival and longevity, in addition to developing new tools to monitor these parameters, is paramount. Using both a mouse model of GVHD and a mouse model of Type 1 Diabetes (T1D), we describe herein a dual reporter system based on Gluc and multiplexed with SEAP and non-secreted Firefl y luciferase (Fluc), which permits simultaneous imaging and noninvasive tracking of two different T-cell populations (CD4 + CD25 + T-regs and CD4(+)CD25-T-con cells) in vivo by transducing the cells with different lentiviruses bearing distinct color signatures. This new technology promises to overcome the limitations of the conventional methods currently available to study lymphocyte survival in vivo. Furthermore, this novel technique has applications not only in autoimmunity and alloimmunity, but also in the wider fi eld of immunology. C1 [Lewandrowski, Grant K.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Lewandrowski, Grant K.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Magee, Ciara N.; Mounayar, Marwan; Azzi, Jamil] Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Div,Transplantat Res Ctr, Boston, MA 02115 USA. [Magee, Ciara N.; Mounayar, Marwan; Azzi, Jamil] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Lewandrowski, GK (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. NR 35 TC 4 Z9 4 U1 0 U2 17 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 211 EP 227 DI 10.1007/978-1-62703-718-1_17 D2 10.1007/978-1-62703-718-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700018 PM 24166380 ER PT S AU van Rijn, S Wurdinger, T Nilsson, J AF van Rijn, Sjoerd Wuerdinger, Thomas Nilsson, Jonas BE Badr, CE TI Multiplex Functional Bioluminescent Reporters Using Gaussia Luciferase Fused to Epitope Tags in an Immunobinding Assay SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Gaussia luciferase; Optical imaging; Bioluminescent imaging; Multiplex assay; Epitope tag; Antibody binding assay ID GENE-EXPRESSION; IN-VIVO; APOPTOSIS; SYSTEM AB The use of Gaussia luciferase in a multiplex assay can have several advantages over the singleplex method for an experimental setup. Issues such as intersample variability, screening purposes, efficiency, and in vivo applications can be addressed using a multiplex assay. Here we describe a functional reporter multiplex method using Gaussia luciferase fused to epitope tags to identify the different reporters that are expressed. Tag specific antibodies are used to bind and separate the tagged luciferase reporters. C1 [van Rijn, Sjoerd; Wuerdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Wuerdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Wuerdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Nilsson, Jonas] Umea Univ, Dept Radiat Sci, Umea, Sweden. RP van Rijn, S (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. NR 12 TC 2 Z9 2 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 231 EP 247 DI 10.1007/978-1-62703-718-1_18 D2 10.1007/978-1-62703-718-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700019 PM 24166381 ER PT S AU Lai, CP Tannous, BA Breakefield, XO AF Lai, Charles P. Tannous, Bakhos A. Breakefield, Xandra O. BE Badr, CE TI Noninvasive In Vivo Monitoring of Extracellular Vesicles SO BIOLUMINESCENT IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Extracellular vesicles; Microvesicles; Exosomes; Gaussia luciferase; Bioluminescence; Coelenterazine ID EXOSOMES; CELLS; MICROVESICLES; MECHANISM; EXPRESSION; MICRORNAS; PROTEINS; CURCUMIN; DELIVERY; GROWTH AB Extracellular vesicles (EVs) including exosomes and microvesicles are nanometer-sized vesicles released by cells to deliver lipids, cellular proteins, mRNAs, and noncoding RNAs, thereby facilitating intercellular communication without direct cell-to-cell contacts. Due to their nanoscale size, EVs have been visualized under microscopy in vitro. We here describe a strategy to label EVs with Gaussia luciferase for noninvasive bioluminescence imaging and monitoring of systemically administered EVs in vivo. C1 [Lai, Charles P.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Boston, MA 02129 USA. [Lai, Charles P.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Lai, CP (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Boston, MA 02129 USA. RI Lai, Charles/D-5442-2017 FU Canadian Institutes of Health Research; NCI NIH HHS [CA141150, P01 CA069246]; NINDS NIH HHS [P30 NS045776] NR 32 TC 8 Z9 8 U1 1 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-717-4; 978-1-62703-718-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1098 BP 249 EP 258 DI 10.1007/978-1-62703-718-1_19 D2 10.1007/978-1-62703-718-1 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BJJ04 UT WOS:000328378700020 PM 24166382 ER PT J AU Tabatabaei, N Kang, D Wu, T Kim, M Carruth, RW Leung, J Sauk, JS Shreffler, W Yuan, Q Katz, A Nishioka, NS Tearney, GJ AF Tabatabaei, Nima Kang, DongKyun Wu, Tao Kim, Minkyu Carruth, Robert W. Leung, John Sauk, Jenny S. Shreffler, Wayne Yuan, Qian Katz, Aubrey Nishioka, Norman S. Tearney, Guillermo J. TI Tethered confocal endomicroscopy capsule for diagnosis and monitoring of eosinophilic esophagitis SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID LASER ENDOMICROSCOPY; MICROSCOPY; ADULTS; PROBE AB Eosinophilic esophagitis (EoE) is an allergic condition that is characterized by eosinophils infiltrating the esophageal wall. The treatment of the disease may require multiple follow up sedated endoscopies and biopsies to confirm elimination of eosinophils. These procedures are expensive, time consuming, and may be difficult for patients to tolerate. Here we report on the development of a confocal microscopy capsule for diagnosis and monitoring of EoE. The swallowable capsule implements a high-speed fiber-based reflectance confocal microscopy technique termed Spectrally Encoded Confocal Microscopy (SECM). SECM scans the sample in one dimension without moving parts by using wavelength swept source illumination and a diffraction grating at the back plane of the objective lens. As the wavelength of the source is tuned, the SECM optics within the 7 x 30 mm capsule are rotated using a driveshaft enclosed in a 0.8 mm flexible tether. A single rotation of the optics covered a field of view of 22 mm x 223 mu m. The lateral and axial resolutions of the device were measured to be 2.1 and 14 mu m, respectively. Images of Acetic Acid stained swine esophagus obtained with the capsule ex vivo and in vivo clearly showed squamous epithelial nuclei, which are smaller and less reflective than eosinophils. Imaging of esophageal biopsies from EoE patients ex vivo demonstrated the capability of this technology to visualize individual eosinophils. Based on the results of this study, we believe that this capsule will be a simpler and more effective device for diagnosing EoE and monitoring the therapeutic response of this disease. (C) 2013 Optical Society of America C1 [Tabatabaei, Nima; Kang, DongKyun; Wu, Tao; Kim, Minkyu; Carruth, Robert W.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tabatabaei, Nima; Kang, DongKyun; Wu, Tao; Kim, Minkyu; Carruth, Robert W.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Minkyu] Univ Tokyo, Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan. [Leung, John; Shreffler, Wayne] Harvard Univ, Food Allergy Ctr, Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leung, John; Shreffler, Wayne] Harvard Univ, Massachusetts Gen Hosp, Med Sch, Boston, MA 02114 USA. [Sauk, Jenny S.; Nishioka, Norman S.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Yuan, Qian; Katz, Aubrey] Harvard Univ, Dept Pediat, Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Dept Pathol, Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tabatabaei, N (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM gtearney@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases [5R01DK091923- 02]; Natural Sciences and Engineering Research Council of Canada (NSERC) FX This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant (5R01DK091923- 02, PI: G. Tearney). N.T. is thankful to the Natural Sciences and Engineering Research Council of Canada (NSERC) for a post-doctoral fellowship award. NR 26 TC 4 Z9 4 U1 2 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JAN 1 PY 2014 VL 5 IS 1 BP 197 EP 207 DI 10.1364/BOE.5.5.000197 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 283DN UT WOS:000329225500017 ER PT J AU Cho, HS Jang, SJ Kim, K Dan-Chin-Yu, AV Shishkov, M Bouma, BE Oh, WY AF Cho, Han Saem Jang, Sun-Joo Kim, Kyunghun Dan-Chin-Yu, Alexey V. Shishkov, Milen Bouma, Brett E. Oh, Wang-Yuhl TI High frame-rate intravascular optical frequency-domain imaging in vivo SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID COHERENCE TOMOGRAPHY; MICROSCOPY; ULTRASOUND; 2ND AB Intravascular optical frequency-domain imaging (OFDI), a second-generation optical coherence tomography (OCT) technology, enables imaging of the three-dimensional (3D) microstructure of the vessel wall following a short and nonocclusive clear liquid flush. Although 3D vascular visualization provides a greater appreciation of the vessel wall and intraluminal structures, a longitudinal imaging pitch that is several times bigger than the optical imaging resolution of the system has limited true high-resolution 3D imaging, mainly due to the slow scanning speed of previous imaging catheters. Here, we demonstrate high frame-rate intravascular OFDI in vivo, acquiring images at a rate of 350 frames per second. A custom-built, high-speed, and high-precision fiber-optic rotary junction provided uniform and high-speed beam scanning through a custom-made imaging catheter with an outer diameter of 0.87 mm. A 47-mm-long rabbit aorta was imaged in 3.7 seconds after a short contrast agent flush. The longitudinal imaging pitch was 34 mu m, comparable to the transverse imaging resolution of the system. Three-dimensional volumerendering showed greatly enhanced visualization of tissue microstructure and stent struts relative to what is provided by conventional intravascular imaging speeds. (C) 2013 Optical Society of America C1 [Cho, Han Saem; Jang, Sun-Joo; Kim, Kyunghun; Oh, Wang-Yuhl] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea. [Jang, Sun-Joo] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Kim, Kyunghun] Korea Adv Inst Sci & Technol, Dept Comp Sci, Taejon 305701, South Korea. [Dan-Chin-Yu, Alexey V.] Hyunjoo In Tech, Seoul 152790, South Korea. [Shishkov, Milen; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Shishkov, Milen; Bouma, Brett E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cho, HS (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea. EM woh1@kaist.ac.kr FU NRF of Korea [2010-0017465]; MSIP of Korea [CISS-2012M3A6A6054200, NIPA-2013-H0401-13-1007]; NIH [P41 EB015903] FX This research was supported in part by the NRF of Korea, grant 2010-0017465, by the MSIP of Korea, grant GFP/(CISS-2012M3A6A6054200) and grant NIPA-2013-H0401-13-1007, and by the NIH, grant P41 EB015903. NR 21 TC 14 Z9 14 U1 0 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JAN 1 PY 2014 VL 5 IS 1 BP 223 EP 232 DI 10.1364/BOE.5.5.000223 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 283DN UT WOS:000329225500019 PM 24466489 ER PT J AU Huober, J Cole, BF Rabaglio, M Giobbie-Hurder, A Wu, J Ejlertsen, B Bonnefoi, H Forbes, JF Neven, P Lang, I Smith, I Wardley, A Price, KN Goldhirsch, A Coates, AS Colleoni, M Gelber, RD Thurlimann, B AF Huober, J. Cole, B. F. Rabaglio, M. Giobbie-Hurder, A. Wu, J. Ejlertsen, B. Bonnefoi, H. Forbes, J. F. Neven, P. Lang, I. Smith, I. Wardley, A. Price, K. N. Goldhirsch, A. Coates, A. S. Colleoni, M. Gelber, R. D. Thuerlimann, B. CA BIG 1-98 Collaborative Grp Int Breast Canc Study Grp TI Symptoms of endocrine treatment and outcome in the BIG 1-98 study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aromatase inhibitor; Side effects; Breast cancer; Endocrine therapy ID BREAST-CANCER-TREATMENT; ADVERSE EVENTS; POSTMENOPAUSAL WOMEN; CYP2D6 GENOTYPE; RETROSPECTIVE ANALYSIS; TAMOXIFEN METABOLISM; AROMATASE INHIBITORS; COMPETING RISK; ATAC TRIAL; RECURRENCE AB There may be a relationship between the incidence of vasomotor and arthralgia/myalgia symptoms and treatment outcomes for postmenopausal breast cancer patients with endocrine-responsive disease who received adjuvant letrozole or tamoxifen. Data on patients randomized into the monotherapy arms of the BIG 1-98 clinical trial who did not have either vasomotor or arthralgia/myalgia/carpal tunnel (AMC) symptoms reported at baseline, started protocol treatment and were alive and disease-free at the 3-month landmark (n = 4,798) and at the 12-month landmark (n = 4,682) were used for this report. Cohorts of patients with vasomotor symptoms, AMC symptoms, neither, or both were defined at both 3 and 12 months from randomization. Landmark analyses were performed for disease-free survival (DFS) and for breast cancer free interval (BCFI), using regression analysis to estimate hazard ratios (HR) and 95 % confidence intervals (CI). Median follow-up was 7.0 years. Reporting of AMC symptoms was associated with better outcome for both the 3- and 12-month landmark analyses [e.g., 12-month landmark, HR (95 % CI) for DFS = 0.65 (0.49-0.87), and for BCFI = 0.70 (0.49-0.99)]. By contrast, reporting of vasomotor symptoms was less clearly associated with DFS [12-month DFS HR (95 % CI) = 0.82 (0.70-0.96)] and BCFI (12-month DFS HR (95 % CI) = 0.97 (0.80-1.18). Interaction tests indicated no effect of treatment group on associations between symptoms and outcomes. While reporting of AMC symptoms was clearly associated with better DFS and BCFI, the association between vasomotor symptoms and outcome was less clear, especially with respect to breast cancer-related events. C1 [Huober, J.; Thuerlimann, B.] Kantonsspital St Gallen, Breast Ctr, St Gallen, Switzerland. [Huober, J.; Thuerlimann, B.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Huober, J.] Univ Ulm, Dept Gynecol, D-89075 Ulm, Germany. [Cole, B. F.; Wu, J.] Univ Vermont, Dept Math & Stat, Coll Engn & Math Sci, Burlington, VT 05405 USA. [Cole, B. F.; Giobbie-Hurder, A.; Price, K. N.; Gelber, R. D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02215 USA. [Rabaglio, M.; Coates, A. S.] Int Breast Canc Study Grp, Bern, Switzerland. [Rabaglio, M.] Univ Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Ejlertsen, B.] Copenhagen Univ Hosp, Rigshosp, Danish Breast Canc Cooperat Grp DBCG Stat Ctr, Copenhagen, Denmark. [Ejlertsen, B.] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Bonnefoi, H.] Univ Bordeaux, Inst Bergonie, Dept Med Oncol, INSERM U916,FNCLCC Unicanc, Bordeaux, France. [Forbes, J. F.] Univ Newcastle, Australia & New Zealand Breast Canc Trials Grp, Calvary Mater Newcastle, Newcastle, NSW 2300, Australia. [Neven, P.] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. [Lang, I.] Natl Inst Oncol, Budapest, Hungary. [Smith, I.] Royal Marsden Hosp, London SW3 6JJ, England. [Wardley, A.] South Manchester Univ Hosp Trust, Christie Hosp NHS Trust, Manchester, Lancs, England. [Price, K. N.; Gelber, R. D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Goldhirsch, A.] European Inst Oncol, Dept Med, Milan, Italy. [Coates, A. S.] Univ Sydney, Sydney, NSW 2006, Australia. [Colleoni, M.] European Inst Oncol, Dept Med, Res Unit Med Senol, Milan, Italy. [Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gelber, R. D.] Harvard Univ, Sch Med, Boston, MA USA. RP Huober, J (reprint author), Kantonsspital St Gallen, Breast Ctr, St Gallen, Switzerland. EM Jens.Huober@uniklinik-ulm.de; price@jimmy.harvard.edu RI Wardley, ANdrew/N-8135-2015 OI Wardley, ANdrew/0000-0002-9639-0888 FU Novartis; Swedish Cancer Society; Cancer Council Australia; Australia and New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute Grant [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX The BIG 1-98 trial was sponsored by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society, The Cancer Council Australia, Australia and New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), the National Cancer Institute Grant CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). NR 36 TC 10 Z9 11 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2014 VL 143 IS 1 BP 159 EP 169 DI 10.1007/s10549-013-2792-7 PG 11 WC Oncology SC Oncology GA 284DE UT WOS:000329295500016 PM 24305979 ER PT J AU Verbeek, FPR Troyan, SL Mieog, JSD Liefers, GJ Moffitt, LA Rosenberg, M Hirshfield-Bartek, J Gioux, S van de Velde, CJH Vahrmeijer, AL Frangioni, JV AF Verbeek, Floris P. R. Troyan, Susan L. Mieog, J. Sven D. Liefers, Gerrit-Jan Moffitt, Lorissa A. Rosenberg, Mireille Hirshfield-Bartek, Judith Gioux, Sylvain van de Velde, Cornelis J. H. Vahrmeijer, Alexander L. Frangioni, John V. TI Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Near-infrared fluorescence; Breast cancer; Sentinel lymph node mapping; Indocyanine green ID INDOCYANINE GREEN FLUORESCENCE; BLUE-DYE; NAVIGATION SURGERY; CLINICAL-TRIAL; BIOPSY; DISSECTION AB Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the sentinel lymph node (SLN) procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 mL of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of NIR fluorescence for SLN mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using (99)Technetium-colloid in all subjects and patent blue in 27 (28 %) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99 %) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean 1.9, range 1-5) were resected: 100 % NIR fluorescent, 88 % radioactive, and 78 % (of 40 nodes) blue. In 2 of 95 subjects (2.1 %), SLNs-containing macrometastases were found only by NIR fluorescence, and in one patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies. C1 [Verbeek, Floris P. R.; Mieog, J. Sven D.; Liefers, Gerrit-Jan; van de Velde, Cornelis J. H.; Vahrmeijer, Alexander L.] Leiden Univ, Med Ctr, Dept Surg, NL-2300 RC Leiden, Netherlands. [Troyan, Susan L.; Hirshfield-Bartek, Judith] Dana Farber Brigham & Womens Canc Ctr, Dept Surg, Boston, MA USA. [Moffitt, Lorissa A.; Rosenberg, Mireille; Gioux, Sylvain; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Vahrmeijer, AL (reprint author), Leiden Univ, Med Ctr, Dept Surg, Albinusdreef 2, NL-2300 RC Leiden, Netherlands. EM a.l.vahrmeijer@lumc.nl FU Leiden University Fund/Piso Kuperus; Netherlands Organization for Health Research and Development [92003526]; Centre for Translational Molecular Medicine, project MUSIS [03O-202]; Nuts Ohra Fund; Dutch Cancer Society [UL2010-4732]; National Institutes of Health [R21-CA-130297, R01-CA-115296] FX The authors thank Alan Stockdale, Dr. Vivek Venugopal, Florin Neacsu, Frank W. Kettenring, Dr. Yoshitomo Ashitate, Dr. Summer Gibbs, and Yang (Allison) Xie for operation of the Mini-FLARE imaging system, and David J. Burrington, Jr. for editing. F. P. R. Verbeek's travel to Boston for completion of the trials was sponsored by the Leiden University Fund/Piso Kuperus. J. S. D. Mieog is a MD-medical research trainee funded by The Netherlands Organization for Health Research and Development (Grant No. 92003526). This study was performed within the framework of the Centre for Translational Molecular Medicine, project MUSIS (grant 03O-202), and was funded by the Nuts Ohra Fund, Dutch Cancer Society grant UL2010-4732 and National Institutes of Health grants R21-CA-130297 and R01-CA-115296. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 35 TC 54 Z9 57 U1 7 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2014 VL 143 IS 2 BP 333 EP 342 DI 10.1007/s10549-013-2802-9 PG 10 WC Oncology SC Oncology GA 285AG UT WOS:000329364200012 PM 24337507 ER PT J AU Wong, JS Chen, YH Gadd, MA Gelman, R Lester, SC Schnitt, SJ Sgroi, DC Silver, BJ Smith, BL Troyan, SL Harris, JR AF Wong, Julia S. Chen, Yu-Hui Gadd, Michele A. Gelman, Rebecca Lester, Susan C. Schnitt, Stuart J. Sgroi, Dennis C. Silver, Barbara J. Smith, Barbara L. Troyan, Susan L. Harris, Jay R. TI Eight-year update of a prospective study of wide excision alone for small low- or intermediate-grade ductal carcinoma in situ (DCIS) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Ductal carcinoma in situ; Local recurrence; Wide excision ID BREAST-CONSERVING THERAPY; SURGICAL ADJUVANT BREAST; LOCAL RECURRENCE; MARGIN WIDTH; RISK; CANCER; OUTCOMES; SURGERY; WOMEN; RADIOTHERAPY AB Whether wide excision with margins a parts per thousand yen1 cm is sufficient treatment for small low- or intermediate-grade ductal carcinoma in situ (DCIS) is unclear. This is an updated analysis of a phase II, single-arm, prospective trial testing this hypothesis. A total of 158 patients with low- or intermediate-grade DCIS who underwent wide excision alone (without radiation or tamoxifen) were entered onto the trial from 1995 to 2002. Entry criteria included mammographic extent a parts per thousand currency sign2.5 cm, predominantly low or intermediate nuclear grade, and excision with final microscopic margins a parts per thousand yen1 cm. Eight-year minimum potential follow-up was required for inclusion in the analysis; the final population comprised 143 patients. Cumulative incidence curves were generated to assess rates of local recurrence (LR) or other events. Median follow-up time was 11 years. Nineteen patients (13 %) had LR as a first event within 8 years. Thirteen LR (68 %) were DCIS only and six (32 %) were invasive. Fourteen (74 %) occurred in the original quadrant. The 10-year estimated cumulative incidence of LR was 15.6 %. The estimated annual percentage rate of LR was 1.9 % per patient-year. With longer follow-up, there remains a substantial and ongoing risk of LR in patients with favorable DCIS treated with wide excision margins without radiation. This information should be useful as patients and clinicians weigh the options of wide excision with and without radiation. C1 [Wong, Julia S.; Silver, Barbara J.; Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Wong, Julia S.; Chen, Yu-Hui; Gadd, Michele A.; Gelman, Rebecca; Lester, Susan C.; Schnitt, Stuart J.; Sgroi, Dennis C.; Silver, Barbara J.; Smith, Barbara L.; Troyan, Susan L.; Harris, Jay R.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yu-Hui; Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gadd, Michele A.; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lester, Susan C.] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Troyan, Susan L.] Brigham & Womens Hosp, Dept Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wong, JS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM jwong@lroc.harvard.edu NR 30 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2014 VL 143 IS 2 BP 343 EP 350 DI 10.1007/s10549-013-2813-6 PG 8 WC Oncology SC Oncology GA 285AG UT WOS:000329364200013 PM 24346130 ER PT J AU Tsao, H AF Tsao, H. TI Opening the melanoma black box SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID MUTATIONS C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM htsao@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2014 VL 170 IS 1 BP 9 EP 10 PG 2 WC Dermatology SC Dermatology GA 287GO UT WOS:000329530200077 PM 24443911 ER PT J AU Fong, ZV Tanabe, KK AF Fong, Z. V. Tanabe, K. K. TI Comparison of melanoma guidelines in the USA, Canada, Europe, Australia and New Zealand: a critical appraisal and comprehensive review SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Review ID CUTANEOUS MALIGNANT-MELANOMA; GENOME-WIDE ASSOCIATION; SUN EXPOSURE; SKIN-CANCER; RISK-FACTORS; UNITED-STATES; PIGMENTARY CHARACTERISTICS; ATTRIBUTABLE FRACTION; INCREASING INCIDENCE; PARKINSON-DISEASE AB There are several well-established guidelines for the staging of melanoma and the size of excisional margins, along with recommendations for sentinel lymph node biopsy. Guidelines have been proposed in the U.S.A. (National Comprehensive Cancer Network), Canada (Cancer Care Ontario and Canadian Medical Association), Europe (European Society for Medical Oncology) and Australia and New Zealand (Australian Cancer Network). The guidelines set by these groups are largely based on current evidence, or expert panel consensus where evidence is lacking. The recommendations are more controversial and varying where there is a lack of level-one evidence in the literature (e.g. screening, adjuvant therapy, follow-up intensity). We review the evidence and available literature for the management of melanoma worldwide. C1 [Fong, Z. V.; Tanabe, K. K.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Surg Oncol, Boston, MA 02115 USA. RP Tanabe, KK (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Surg Oncol, Boston, MA 02115 USA. EM ktanabe@partners.org NR 91 TC 23 Z9 24 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2014 VL 170 IS 1 BP 20 EP 30 PG 11 WC Dermatology SC Dermatology GA 287GO UT WOS:000329530200072 PM 24116870 ER PT J AU Sullivan, RJ Flaherty, KT AF Sullivan, R. J. Flaherty, K. T. TI Major therapeutic developments and current challenges in advanced melanoma SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; CUTANEOUS MALIGNANT-MELANOMA; PIGMENTED SKIN-LESIONS; MELANOCYTIC NEVI; HISTOPATHOLOGIC DIAGNOSIS; BRAF MUTATIONS; EXPRESSION; GENE; BENIGN; MARKER AB Malignant melanoma is rising in incidence. The treatment options have been very limited but advances in molecular biology and immunology have led to a greater understanding of the pathogenesis of the disease. Four drugs have been approved for the treatment of advanced melanoma in the past 2 years and two new classes of agents have recently been shown to lead to durable responses in a substantial minority of patients. The identification of biomarkers has helped clinicians and researchers segregate patients into molecular subgroups, which facilitates the selection of therapy. Preliminary work has begun on determining the ideal sequences of the various therapies. Investigations have been carried out on why these treatments work and what the mechanisms of resistance are to these therapies. It is hoped that combinations of therapies will emerge that lead to a high percentage of durable responses. C1 [Sullivan, R. J.; Flaherty, K. T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM rsullivan7@partners.org NR 43 TC 16 Z9 16 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2014 VL 170 IS 1 BP 36 EP 44 DI 10.1111/bjd.12698 PG 9 WC Dermatology SC Dermatology GA 287GO UT WOS:000329530200020 PM 24443912 ER PT J AU Deininger, MW Kopecky, KJ Radich, JP Kamel-Reid, S Stock, W Paietta, E Emanuel, PD Tallman, M Wadleigh, M Larson, RA Lipton, JH Slovak, ML Appelbaum, FR Druker, BJ AF Deininger, Michael W. Kopecky, Kenneth J. Radich, Jerald P. Kamel-Reid, Suzanne Stock, Wendy Paietta, Elisabeth Emanuel, Peter D. Tallman, Martin Wadleigh, Martha Larson, Richard A. Lipton, Jeffrey H. Slovak, Marilyn L. Appelbaum, Frederick R. Druker, Brian J. TI Imatinib 800 mg daily induces deeper molecular responses than imatinib 400 mg daily: results of SWOG S0325, an intergroup randomized PHASE II trial in newly diagnosed chronic phase chronic myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE BCR-ABL1; chronic myeloid leukaemia; imatinib ID INTERFERON-ALPHA; TYROSINE KINASE; FOLLOW-UP; DASATINIB; MESYLATE; INHIBITOR; NILOTINIB; EFFICACY; THERAPY; SAFETY AB The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukaemia (CP-CML) is 400mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematological and cytogenetic response to IM400 vs. imatinib 400mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P=0038; 3-log reduction: 53% vs. 35%, P=0049). During the first 12months BCR-ABL1 levels in the IM800 arm were an average 29-fold lower than in the IM400 arm (P=0010). Complete haematological response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P=0040). Grade 3-4 toxicities were more common for IM800 (58% vs. 31%, P=00007), and were most commonly haematological. Few patients have relapsed, progressed or died, but both progression-free (P=0048) and relapse-free (P=0031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper MRs than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. C1 [Deininger, Michael W.; Druker, Brian J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kopecky, Kenneth J.] SWOG Stat Ctr, Seattle, WA USA. [Kopecky, Kenneth J.; Radich, Jerald P.; Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kamel-Reid, Suzanne] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Stock, Wendy; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Paietta, Elisabeth] Montefiore Med Ctr, Bronx, NY 10467 USA. [Emanuel, Peter D.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Tallman, Martin] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lipton, Jeffrey H.] Princess Margaret Hosp, Univ Hlth Network OCI, Toronto, ON M4X 1K9, Canada. [Slovak, Marilyn L.] City Hope Natl Med Ctr, Duarte, CA USA. RP Deininger, MW (reprint author), Univ Utah, Huntsman Canc Inst, 2000 Circle Hope,Room 4280, Salt Lake City, UT 84112 USA. EM michael.deininger@hci.utah.edu OI Emanuel, Peter/0000-0002-9764-2434; Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute, DHHS [CA32102, CA38926, CA35261, CA35431, CA27057, CA13238, CA45807, CA58882, CA67575, CA46113, CA46368, CA12644, CA45808, CA20319, CA35128, CA35176, CA11083, CA76462, CA46282, CA35119, CA04919, CA63848, CA37981, CA16385, CA22433, CA35090, CA31946, CA41287]; Bristol-Myers Squibb. Michael W Deininger is a Scholar in Clinical Research of the Leukemia & Lymphoma Society FX We thank Patricia Arlauskas, SWOG Publications Office, for editorial assistance. This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA35261; CA35431; CA27057; CA13238; CA45807; CA58882; CA67575; CA46113, CA46368, CA12644, CA45808, CA20319, CA35128, CA35176, CA11083, CA76462, CA46282, CA35119, CA04919, CA63848, CA37981, CA16385, CA22433, CA35090, CA31946, CA41287; and in part by Bristol-Myers Squibb. Michael W Deininger is a Scholar in Clinical Research of the Leukemia & Lymphoma Society. NR 30 TC 17 Z9 18 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2014 VL 164 IS 2 BP 223 EP 232 DI 10.1111/bjh.12618 PG 10 WC Hematology SC Hematology GA 282NH UT WOS:000329178100009 PM 24383843 ER PT J AU Fanale, M Assouline, S Kuruvilla, J Solal-Celigny, P Heo, DS Verhoef, G Corradini, P Abramson, JS Offner, F Engert, A Dyer, MJS Carreon, D Ewald, B Baeck, J Younes, A Freedman, AS AF Fanale, Michelle Assouline, Sarit Kuruvilla, John Solal-Celigny, Philippe Heo, Dae S. Verhoef, Gregor Corradini, Paolo Abramson, Jeremy S. Offner, Fritz Engert, Andreas Dyer, Martin J. S. Carreon, Daniel Ewald, Brett Baeck, Johan Younes, Anas Freedman, Arnold S. TI Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE non-Hodgkin lymphoma; Hodgkin lymphoma; monoclonal antibodies ID CHRONIC LYMPHOCYTIC-LEUKEMIA; REED-STERNBERG CELLS; ANTIGEN-EXPRESSION; ANTI-CD40; DACETUZUMAB; RITUXIMAB; DISEASE; EFFICACY; CRITERIA; LIGAND AB Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4mg/kg of lucatumumab. A total of 111 patients with NHL (n=74) and HL (n=37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33.3% and 42.9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation. C1 [Fanale, Michelle] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Assouline, Sarit] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Kuruvilla, John] Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. [Solal-Celigny, Philippe] Inst Cancerol Ouest, Nantes, France. [Heo, Dae S.] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Verhoef, Gregor] Univ Hosp Leuven, Dept Haematol, Louvain, Belgium. [Corradini, Paolo] Univ Milan, IRCCS Natl Canc Inst, Milan, Italy. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [Offner, Fritz] Ghent Univ Hosp, Dept Haematol, Ghent, Belgium. [Engert, Andreas] Univ Hosp Cologne, Cologne, Germany. [Dyer, Martin J. S.] Univ Leicester, Dept Canc Studies & Mol Med, Leicester, Leics, England. [Carreon, Daniel; Ewald, Brett; Baeck, Johan] Novartis Pharmaceut, E Hanover, NJ USA. [Younes, Anas] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM arnold_freedman@dfci.harvard.edu RI Dyer, Martin/F-2691-2014; OI Dyer, Martin/0000-0002-5033-2236; Corradini, Paolo/0000-0002-9186-1353 FU Novartis Pharmaceuticals FX Financial support for this study was provided by Novartis Pharmaceuticals. We thank William Fazzone, PhD, for medical editorial assistance with this manuscript. All authors have substantially contributed to research design or acquired, analysed or interpreted data, as well as drafted and approved the manuscript. In addition, JB, AY, and AF designed the research study; MF, SA, JK, PS-C, PC, JA, FO, MD, JB, AY, and AF performed research; MF, PS-C, JB, and AF analysed the data; MF, PS-C, JB, and AF wrote the paper. NR 27 TC 24 Z9 26 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2014 VL 164 IS 2 BP 258 EP 265 DI 10.1111/bjh.12630 PG 8 WC Hematology SC Hematology GA 282NH UT WOS:000329178100013 PM 24219359 ER PT J AU Khan, MAS Sahani, N Neville, KA Nagashima, M Lee, S Sasakawa, T Kaneki, M Martyn, JAJ AF Khan, Mohammed A. S. Sahani, Nita Neville, Kevin A. Nagashima, Michio Lee, Sangseok Sasakawa, Tomoki Kaneki, Masao Martyn, J. A. Jeevendra TI Nonsurgically induced disuse muscle atrophy and neuromuscular dysfunction upregulates alpha7 acetylcholine receptors SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE alpha 7 acetylcholine receptors; external plastic casting; immobilization; muscle atrophy; neuromuscular dysfunction ID SKELETAL-MUSCLE; HINDLIMB IMMOBILIZATION; BED REST; D-TUBOCURARINE; MICE; EXPRESSION; RATS; DENERVATION; MECHANISMS; RECOVERY AB Previous models of muscle disuse have invariably used surgical methods that require the repetitive application of plaster casts. A method of disuse atrophy that does not require such repetitive applications is described herein. Modified plastic pipette tubing was applied to a single hindlimb (mouse), from thigh to foot, resulting in immobilization of the knee in the extension position, and the ankle in the plantar flexion position. This method resulted in the loss of soleus muscle to 11%, 22%, 39%, and 45% of its original mass at 3, 7, 14, and 21 days, respectively, in association with a significant decrease of tibialis twitch (25%) and tetanic tensions (26%) at 21 days, compared with the contralateral side and (or) sham-immobilized controls. Immunohistochemical analysis of the soleus using fluorescent alpha-bungarotoxin revealed a significant increase in the number of synapses per unit area (818 + 31 compared with 433 + 16/mm(2)) and an increase in muscle fibers per unit area (117 compared with 83/mm(2)), most likely related to the atrophy of muscle fibers bringing synapses closer. A 3-fold increase in alpha7 acetylcholine receptor (alpha 7AChR) protein expression, along with increased expression of alpha 1AChR subunit in the immobilized side compared with the contralateral side was observed. The physiology and pharmacology of the novel finding of upregulation of alpha 7AChRs with disuse requires further study. C1 [Khan, Mohammed A. S.; Sahani, Nita; Neville, Kevin A.; Nagashima, Michio; Lee, Sangseok; Sasakawa, Tomoki; Kaneki, Masao; Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Shriners Hosp Children, Boston, MA 02114 USA. [Khan, Mohammed A. S.; Sahani, Nita; Neville, Kevin A.; Nagashima, Michio; Lee, Sangseok; Sasakawa, Tomoki; Kaneki, Masao; Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Shriners Hosp Children, Boston, MA 02114 USA. EM jmartyn@partners.org OI Lee, Sangseok/0000-0001-7023-3668; Nagashima, Michio/0000-0001-7416-5367 FU National Institutes for Health [NIH RO1-055082, P50-25000]; Shriners Hospitals for Children Research Philanthropy FX This work was supported with grants from the National Institutes for Health (NIH RO1-055082) and P50-25000 project IV and from Shriners Hospitals for Children Research Philanthropy to J.A.J.M. We thank Dr. Hui Zheng for his advice on statistical analyses. NR 32 TC 3 Z9 5 U1 1 U2 2 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 1200 MONTREAL ROAD, BUILDING M-55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4212 EI 1205-7541 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD JAN PY 2014 VL 92 IS 1 BP 1 EP 8 DI 10.1139/cjpp-2013-0063 PG 8 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 283AF UT WOS:000329215800002 PM 24383867 ER PT J AU Hasty, P Livi, CB Dodds, SG Jones, D Strong, R Javors, M Fischer, KE Sloane, L Murthy, K Hubbard, G Sun, LS Hurez, V Curiel, TJ Sharp, ZD AF Hasty, Paul Livi, Carolina B. Dodds, Sherry G. Jones, Diane Strong, Randy Javors, Martin Fischer, Kathleen E. Sloane, Lauren Murthy, Kruthi Hubbard, Gene Sun, Lishi Hurez, Vincent Curiel, Tyler J. Sharp, Zelton Dave TI eRapa Restores a Normal Life Span in a FAP Mouse Model SO CANCER PREVENTION RESEARCH LA English DT Article ID GENETICALLY HETEROGENEOUS MICE; FAMILIAL ADENOMATOUS POLYPOSIS; MESSENGER-RNA TRANSLATION; PROTEIN S6 KINASE; RAPAMYCIN; CANCERS; CELLS; DYSFUNCTION; RESTRICTION; INHIBITORS AB Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), which confers an extremely high risk for colon cancer. Apc(Min/+) mice exhibit multiple intestinal neoplasia (MIN) that causes anemia and death from bleeding by 6 months. Mechanistic target of rapamycin complex 1 (mTORC1) inhibitors were shown to improve Apc(Min/+) mouse survival when administered by oral gavage or added directly to the chow, but these mice still died from neoplasia well short of a natural life span. The National Institute of Aging Intervention Testing Program showed that enterically targeted rapamycin (eRapa) extended life span for wild-type genetically heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized that eRapa would be effective in preventing neoplasia and extend survival of Apc(Min/+) mice. We show that eRapa improved survival of Apc(Min/+) mice in a dose-dependent manner. Remarkably, and in contrast to previous reports, most of the Apc(Min/+) mice fed 42 parts per million eRapa lived beyond the median life span reported for wild-type syngeneic mice. Furthermore, chronic eRapa did not cause detrimental immune effects in mouse models of cancer, infection, or autoimmunity, thus assuaging concerns that chronic rapamycin treatment suppresses immunity. Our studies suggest that a novel formulation (enteric targeting) of a well-known and widely used drug (rapamycin) can dramatically improve its efficacy in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the dependency on surgery as standard therapy. C1 [Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78145 USA. [Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, San Antonio, TX 78145 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78145 USA. [Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78145 USA. [Fischer, Kathleen E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78145 USA. [Murthy, Kruthi; Sun, Lishi; Hurez, Vincent; Curiel, Tyler J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78145 USA. [Hubbard, Gene] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78145 USA. [Hasty, Paul; Murthy, Kruthi; Curiel, Tyler J.; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78145 USA. [Hasty, Paul; Livi, Carolina B.; Strong, Randy; Fischer, Kathleen E.; Sloane, Lauren; Hubbard, Gene; Curiel, Tyler J.; Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78145 USA. [Strong, Randy] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Sharp, ZD (reprint author), UT Hlth Sci Ctr San Antonio, 15355 Lambda Dr, San Antonio, TX 78145 USA. EM hastye@uthscsa.edu; carolina.livi@Agilent.com; curielt@uthscsa.edu; sharp@uthscsa.edu OI Hurez, Vincent/0000-0003-0271-4157 FU NIH [CA123203, AG017242, RC2AG036613, CA54174, P30-AG013319, CA170491]; Holly Beach Public Library; Voelcker Fund FX This work was supported by the following grants from the NIH: CA123203 and AG017242 (to P. Hasty); RC2AG036613 (to Z.D. Sharp, P. Hasty, R. Strong, and T.J. Curiel); CA54174 (to T.J. Curiel, P. Hasty, and Z.D. Sharp); P30-AG013319 (to R. Strong), CA170491, Holly Beach Public Library, and the Voelcker Fund (T.J. Curiel). NR 50 TC 23 Z9 23 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2014 VL 7 IS 1 BP 169 EP 178 DI 10.1158/1940-6207.CAPR-13-0299 PG 10 WC Oncology SC Oncology GA 285YR UT WOS:000329431500018 PM 24282255 ER PT J AU Cheng, HL Liu, PX Zhang, F Xu, EB Symonds, L Ohlson, CE Bronson, RT Maira, SM Di Tomaso, E Li, J Myers, AP Cantley, LC Mills, GB Zhao, JJ AF Cheng, Hailing Liu, Pixu Zhang, Fan Xu, Erbo Symonds, Lynn Ohlson, Carolynn E. Bronson, Roderick T. Maira, Sauveur-Michel Di Tomaso, Emmanuelle Li, Jane Myers, Andrea P. Cantley, Lewis C. Mills, Gordon B. Zhao, Jean J. TI A Genetic Mouse Model of Invasive Endometrial Cancer Driven by Concurrent Loss of Pten and Lkb1 Is Highly Responsive to mTOR Inhibition SO CANCER RESEARCH LA English DT Article ID MAMMALIAN TARGET; HIGH-FREQUENCY; CARCINOMA; MUTATIONS; PATHWAY; EXPRESSION; KINASE; HYPERPLASIA; SENSITIVITY; ACTIVATION AB Signals from the tumor suppressors PTEN and LKB1 converge on mTOR to negatively regulate its function in cancer cells. Notably, both of these suppressors are attenuated in a significant fraction of human endometrial tumors. In this study, we generated a genetic mouse model of endometrial cancer driven by concomitant loss of these suppressors to gain pathophysiological insight into this disease. Dual loss of Pten and Lkb1 in the endometrial epithelium led to rapid development of advanced endometrioid endometrial tumors with 100% penetrance and short host survival. The tumors displayed dysregulated phosphatidylinositol 3-kinase (PI3K)/Akt and Lkb1/Ampk signaling with hyperactivation of mTOR signaling. Treatment with a dual PI3K/mTOR inhibitor, BEZ235, extended the time before tumor onset and prolonged overall survival. The PI3K inhibitor GDC-0941 used as a single agent reduced the growth rate of primary tumor implants in Pten/Lkb1-deficient mice, and the mTOR inhibitor RAD001 was unexpectedly as effective as BEZ235 in triggering tumor regression. In parallel, we also found that ectopic expression of LKB1 in PTEN/LKB1-deficient human endometrial cancer cells increased their sensitivity to PI3K inhibition. Together, our results demonstrated that Pten/Lkb1-deficient endometrial tumors rely strongly on deregulated mTOR signaling, and they provided evidence that LKB1 status may modulate the response of PTEN-deficient tumors to PI3K or mTOR inhibitors. (C)2013 AACR. C1 [Cheng, Hailing; Liu, Pixu; Xu, Erbo; Symonds, Lynn; Ohlson, Carolynn E.; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA USA. [Myers, Andrea P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Womens Canc,Dept Med Oncol, Boston, MA 02115 USA. [Cheng, Hailing; Liu, Pixu; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Fan; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, DF HCC, Dept Rodent Histopathol Core, Boston, MA USA. [Cheng, Hailing; Zhao, Jean J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Myers, Andrea P.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Di Tomaso, Emmanuelle] Novartis Inst Biomed Res, Cambridge, MA USA. [Li, Jane; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Maira, Sauveur-Michel] Novartis Pharma AG, Oncol Dis Area, Novartis Inst Biomed Res, Basel, Switzerland. RP Zhao, JJ (reprint author), 450 Brookline Ave,Smith 936, Boston, MA 02215 USA. EM hailing_cheng@dfci.harvard.edu; jean_zhao@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU Friends of Dana-Farber Cancer Institute; NIH [CA134502]; Program of the Entertainment Industry Foundation [SU2C-AACR-DT0209]; Stand Up to Cancer Dream Team Translational Research Grant FX This work was supported by Friends of Dana-Farber Cancer Institute (HC) and NIH grants CA134502 (J.J. Zhao). L.C. Cantley, G.B. Mills, and J.J. Zhao are supported by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209). NR 37 TC 16 Z9 18 U1 2 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2014 VL 74 IS 1 BP 15 EP 23 DI 10.1158/0008-5472.CAN-13-0544 PG 9 WC Oncology SC Oncology GA 284DZ UT WOS:000329297600003 PM 24322983 ER PT J AU Krop, I Winer, EP AF Krop, Ian Winer, Eric P. TI Trastuzumab Emtansine: A Novel Antibody-Drug Conjugate for HER2-Positive Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PLUS DOCETAXEL; PHASE-II; LAPATINIB; CHEMOTHERAPY; CAPECITABINE; PI3K AB Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent antimicrotubule agent DM1, linked via a noncleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive (HER2(+)) tumor cell combined with trastuzumab's activation of antibody-dependent cell-mediated cytotoxicity and inhibition of HER2-mediated signal transduction. In phase II studies, T-DM1 was active in patients with trastuzumab-and lapatinib-refractory metastatic breast cancer and led to improved progression-free survival compared with the combination of trastuzumab and docetaxel in the first-line setting. In a recent phase III trial in patients with metastatic breast cancer who previously received trastuzumab and a taxane, T-DM1 resulted in improved progression-free and overall survival compared with capecitabine and lapatinib. T-DM1 is associated with a favorable toxicity profile; reversible thrombocytopenia and hepatic transaminase elevations are the only grade >= 3 adverse event present in 5% or more of patients. Alopecia, peripheral neuropathy, and neutropenia are distinctly uncommon. On the basis of its improved efficacy and toxicity compared with capecitabine/ lapatinib, T-DM1 should be considered the standard for patients with HER2(+) metastatic breast cancer who have previously progressed on trastuzumab and a taxane. Results from additional randomized studies in metastatic breast cancer are pending, and trials in the (neo) adjuvant setting are being initiated. (C) 2013 AACR. C1 [Krop, Ian; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Krop, I (reprint author), Dana Farber Canc Inst, Yawkey 1235,450 Brookline Ave, Boston, MA 02215 USA. EM ikrop@partners.org FU Genentech FX I. Krop has other commercial research support from Genentech and is a consultant/advisory board member of GlaxoSmithKline and Genentech (uncompensated). E. P. Winer has received a commercial research grant from Genentech. NR 25 TC 26 Z9 31 U1 1 U2 27 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2014 VL 20 IS 1 BP 15 EP 20 DI 10.1158/1078-0432.CCR-13-0541 PG 6 WC Oncology SC Oncology GA 284GC UT WOS:000329303100004 PM 24135146 ER PT J AU Wang, XF Haswell, JR Roberts, CWM AF Wang, Xiaofeng Haswell, Jeffrey R. Roberts, Charles W. M. TI Molecular Pathways: SWI/SNF (BAF) Complexes Are Frequently Mutated in Cancer-Mechanisms and Potential Therapeutic Insights SO CLINICAL CANCER RESEARCH LA English DT Article ID CHROMATIN-REMODELING COMPLEX; MALIGNANT RHABDOID TUMORS; ATYPICAL TERATOID/RHABDOID TUMORS; SUPPRESSOR SNF5 LEADS; CELL-CYCLE; ONCOGENIC TRANSFORMATION; HEPATOCELLULAR-CARCINOMA; LUNG ADENOCARCINOMA; SOMATIC MUTATIONS; ARID1A MUTATIONS AB SWI/SNF chromatin remodeling complexes are pleomorphic multisubunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specification, differentiation, and development. Initial clues to a role in tumor suppression for SWI/SNF complexes came over a decade ago when the gene encoding the SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all pediatric rhabdoid tumors. In the last three years, cancer-genome sequencing efforts have revealed an unexpectedly high mutation rate of SWI/SNF subunit genes, which are collectively mutated in 20% of all human cancers and approach the frequency of p53 mutations. Here, we provide a background on these newly recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor suppressor activity, and highlight findings that may lead to potential therapeutic targets for SWI/SNF-mutant cancers. C1 [Wang, Xiaofeng; Haswell, Jeffrey R.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wang, Xiaofeng; Haswell, Jeffrey R.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Wang, Xiaofeng; Haswell, Jeffrey R.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Mayer 657,450 Brookline Ave, Boston, MA 02215 USA. EM charles_roberts@dfci.harvard.edu FU Mouse Models of Cancer Consortium Award [U01 NCI]; Alex's Lemonade Stand Foundation; Hyundai Hope on Wheels; Cure AT/RT Now fund; Garrett B. Smith Foundation; Miles for Mary, and The Ellison Foundation; St. Baldrick's Foundation; Rally Foundation; David Abraham Foundation; [R01CA172152]; [R01CA113794] FX The work in Dr. Roberts' laboratory is partly supported by R01CA172152 (to C.W.M. Roberts) and R01CA113794 (to C.W.M. Roberts), and a U01 NCI Mouse Models of Cancer Consortium Award (C.W.M. Roberts). Alex's Lemonade Stand Foundation, Hyundai Hope on Wheels, the Cure AT/RT Now fund, Garrett B. Smith Foundation, Miles for Mary, and The Ellison Foundation and Cookies for Kids Cancer provided additional support.X. Wang was supported by St. Baldrick's Foundation, the Rally Foundation, and David Abraham Foundation. NR 81 TC 47 Z9 48 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2014 VL 20 IS 1 BP 21 EP 27 DI 10.1158/1078-0432.CCR-13-0280 PG 7 WC Oncology SC Oncology GA 284GC UT WOS:000329303100005 PM 24122795 ER PT J AU Dakhova, O Rowley, D Ittmann, M AF Dakhova, Olga Rowley, David Ittmann, Michael TI Genes Upregulated in Prostate Cancer Reactive Stroma Promote Prostate Cancer Progression In Vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPRESSION ANALYSIS; GROWTH; RECURRENCE; TISSUE; CELLS; BMI1; ANGIOGENESIS; SURVIVAL; BENIGN AB Purpose: Marked reactive stroma formation is associated with poor outcome in clinically localized prostate cancer. We have previously identified genes with diverse functions that are upregulated in reactive stroma. This study tests the hypothesis that expression of these genes in stromal cells enhances prostate cancer growth in vivo. Experimental Design: The expression of reactive stroma genes in prostate stromal cell lines was evaluated by reverse transcriptase (RT)-PCR and qRT-PCR. Genes were knocked down using stable expression of short-hairpin RNAs (shRNA) and the impact on tumorigenesis assessed using the differential reactive stroma (DRS) system, in which prostate stromal cell lines are mixed with LNCaP prostate cancer cells and growth as subcutaneous xenografts assessed. Results: Nine of 10 reactive stroma genes tested were expressed in one or more prostate stromal cell lines. Gene knockdown of c-Kit, Wnt10B, Bmi1, Gli2, orCOMPall resulted in decreased tumorigenesis in the DRS model. In all tumors analyzed, angiogenesis was decreased and there were variable effects on proliferation and apoptosis in the LNCaP cells. Wnt10B has been associated with stem/ progenitor cell phenotype in other tissue types. Using a RT-PCR array, we detected downregulation of multiple genes involved in stem/progenitor cell biology such as OCT4 and LIF as well as cytokines such as VEGFA, BDNF, and CSF2 in cells with Wnt10B knockdown. Conclusions: These findings show that genes upregulated in prostate cancer-reactive stroma promote progression when expressed in prostate stromal cells. Moreover, these data indicate that the DRS model recapitulates key aspects of cancer cell/ reactive stroma interactions in prostate cancer. (C)2013 AACR. C1 [Dakhova, Olga; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Rowley, David] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Ittmann, Michael] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU National Cancer Institute; P30 Cancer Center support grant [P30 CA125123]; Department of Veterans Affairs Merit Review program FX This work was supported by grants from National Cancer Institute to the Tumor Microenvironment Network (1U54CA126568, DR), the P30 Cancer Center support grant (P30 CA125123) to support the Human Tissue Acquisition and Pathology Core, the Department of Veterans Affairs Merit Review program (to M.M. Ittmann) and by the use of the facilities of the Michael E. DeBakey VAMC. NR 33 TC 7 Z9 7 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2014 VL 20 IS 1 BP 100 EP 109 DI 10.1158/1078-0432.CCR-13-1184 PG 10 WC Oncology SC Oncology GA 284GC UT WOS:000329303100013 PM 24150235 ER PT J AU Shapiro, GI Rodon, J Bedell, C Kwak, EL Baselga, J Brana, I Pandya, SS Scheffold, C Laird, AD Nguyen, LT Xu, Y Egile, C Edelman, G AF Shapiro, Geoffrey I. Rodon, Jordi Bedell, Cynthia Kwak, Eunice L. Baselga, Jose Brana, Irene Pandya, Shuchi S. Scheffold, Christian Laird, A. Douglas Nguyen, Linh T. Xu, Yi Egile, Coumaran Edelman, Gerald TI Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245408 (XL147), an Oral Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE PATHWAY; HUMAN CANCER; MUTATIONS; KINASE; TRANSFORMATION; METABOLISM; SIGNALS; TARGET; PIK3CA; TRIAL AB Purpose: SAR245408 is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. This phase I study determined the maximum tolerated dose (MTD) of two dosing schedules [first 21 days of a 28-day period (21/7) and continuous once-daily dosing (CDD)], pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy. Experimental Design: Patients with refractory advanced solid malignancies were treated with SAR245408 using a 3 + 3 design. Pharmacokinetic parameters were determined after single and repeated doses. Pharmacodynamic effects were evaluated in plasma, hair sheath cells, and skin and tumor biopsies. Results: Sixty-nine patients were enrolled. The MTD of both schedules was 600 mg; dose-limiting toxicities were maculopapular rash and hypersensitivity reaction. The most frequent drug-related adverse events included dermatologic toxicities, diarrhea, nausea, and decreased appetite. Plasma pharmacokinetics showed a median time to maximum concentration of 8 to 22 hours, mean terminal elimination half-life of 70 to 88 hours, and 5- to 13-fold accumulation after daily dosing (first cycle). Steady-state concentration was reached between days 15 and 21, and exposure was dose-proportional with doses up to 400 mg. SAR245408 inhibited the PI3K pathway (similar to 40%-80% reduction in phosphorylation of AKT, PRAS40, 4EBP1, and S6 in tumor and surrogate tissues) and, unexpectedly, also inhibited the MEK/ERK pathway. A partial response was seen in one patient with advanced non-small cell lung cancer. Eight patients were progression-free at 6 months. Pharmacodynamic and clinical activity were observed irrespective of tumor PI3K pathway molecular alterations. Conclusions: SAR245408 was tolerable at doses associated with PI3K pathway inhibition. The recommended phase II dose of the capsule formulation is 600 mg administered orally with CDD. (C) 2013 AACR. C1 [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kwak, Eunice L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pandya, Shuchi S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rodon, Jordi; Baselga, Jose; Brana, Irene] Vall dHebron Inst Oncol VHIO, Barcelona, Spain. [Bedell, Cynthia; Edelman, Gerald] Mary Crowley Canc Res Ctr, Dallas, TX USA. [Scheffold, Christian; Laird, A. Douglas; Nguyen, Linh T.] Exelixis Inc, San Francisco, CA USA. [Xu, Yi; Egile, Coumaran] Sanofi, Cambridge, MA USA. [Xu, Yi; Egile, Coumaran] Sanofi, Vitry Sur Seine, France. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Early Drug Dev Ctr, 450 Brookline Ave, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU Exelixis Inc.; Sanofi FX This study was supported by Exelixis Inc. and Sanofi. NR 28 TC 63 Z9 65 U1 5 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2014 VL 20 IS 1 BP 233 EP 245 DI 10.1158/1078-0432.CCR-13-1777 PG 13 WC Oncology SC Oncology GA 284GC UT WOS:000329303100025 PM 24166903 ER PT J AU Adachi, K Coleman, MS Khan, N Jentes, ES Arguin, P Rao, SR LaRocque, RC Sotir, MJ Brunette, G Ryan, ET Meltzer, MI AF Adachi, Kenji Coleman, Margaret S. Khan, Nomana Jentes, Emily S. Arguin, Paul Rao, Sowmya R. LaRocque, Regina C. Sotir, Mark J. Brunette, Gary Ryan, Edward T. Meltzer, Martin I. CA Global TravEpiNet Consortium TI Economics of Malaria Prevention in US Travelers to West Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE costs; benefits; malaria prevention; pretravel health consultation ID COST-EFFECTIVENESS ANALYSIS; INTERNATIONAL TRAVELERS; UNITED-STATES; CHEMOPROPHYLAXIS; PROPHYLAXIS; KENYA AB Background. Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa. Methods. The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature. Results. We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to $372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of $32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country. Conclusions. Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria. C1 [Adachi, Kenji; Coleman, Margaret S.; Khan, Nomana; Jentes, Emily S.; Sotir, Mark J.; Brunette, Gary] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA 30333 USA. [Arguin, Paul] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA. [Rao, Sowmya R.] Univ Massachusetts Med Sch, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [LaRocque, Regina C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meltzer, Martin I.] Ctr Dis Control & Prevent, Div Preparedness & Emerging Infect, Atlanta, GA 30333 USA. RP Coleman, MS (reprint author), Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Natl Ctr Emerging & Zoonot Infect Dis, MS E-03,1600 Clifton Rd, Atlanta, GA 30333 USA. EM mcoleman@cdc.gov FU CDC [U19CI000514, U01CK000175] FX This work was supported by the CDC (Cooperative Agreements U19CI000514 and U01CK000175). NR 27 TC 2 Z9 2 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2014 VL 58 IS 1 BP 11 EP 21 DI 10.1093/cid/cit570 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 280QC UT WOS:000329044800009 PM 24014735 ER PT J AU Kabanda, T Siedner, MJ Klausner, JD Muzoora, C Boulware, DR AF Kabanda, Taseera Siedner, Mark J. Klausner, Jeffrey D. Muzoora, Conrad Boulware, David R. TI Point-of-Care Diagnosis and Prognostication of Cryptococcal Meningitis With the Cryptococcal Antigen Lateral Flow Assay on Cerebrospinal Fluid SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; cryptococcal meningitis; diagnosis; point-of-care; sub-Saharan Africa ID ANTIRETROVIRAL THERAPY; AMPHOTERICIN-B; FLUCONAZOLE; CLEARANCE; BURDEN AB The cryptococcal antigen (CRAG) lateral flow assay (LFA) had 100% sensitivity and specificity on cerebrospinal fluid samples. Pretreatment LFA titers correlated with quantitative cultures (R-2 = 0.7) and predicted 2- and 10-week mortality. The CRAG LFA is an accurate diagnostic assay for CSF and should be considered for point-of-care diagnosis of cryptococcal meningitis. C1 [Kabanda, Taseera; Muzoora, Conrad] Mbarara Univ Sci & Technol, Fac Med, Dept Med, Kampala, Uganda. [Siedner, Mark J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Klausner, Jeffrey D.] Univ Calif Los Angeles, Dept Med, Ctr World Hlth, Los Angeles, CA 90024 USA. [Klausner, Jeffrey D.] Univ Calif Los Angeles, Div Infect Dis, Los Angeles, CA USA. [Boulware, David R.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ5, Boston, MA 02114 USA. EM msiedner@partners.org OI Boulware, David/0000-0002-4715-0060 FU NIAID [U01AI089244, K23AI073192, T32AI007433]; National Institute of Mental Health [K23099916]; Medical Research Council (UK) FX Research and salary support was provided by the NIAID (U01AI089244, K23AI073192, T32AI007433), the National Institute of Mental Health (K23099916), and the Medical Research Council (UK). NR 19 TC 26 Z9 26 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2014 VL 58 IS 1 BP 113 EP 116 DI 10.1093/cid/cit641 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 280QC UT WOS:000329044800025 PM 24065327 ER PT J AU Armah, KA Chang, CCH Baker, JV Ramachandran, VS Budoff, MJ Crane, HM Gibert, CL Goetz, MB Leaf, DA McGinnis, KA Oursler, KK Rimland, D Rodriguez-Barradas, MC Sico, JJ Warner, AL Hsue, PY Kuller, LH Justice, AC Freiberg, MS AF Armah, Kaku A. Chang, Chung-Chou H. Baker, Jason V. Ramachandran, Vasan S. Budoff, Matthew J. Crane, Heidi M. Gibert, Cynthia L. Goetz, Matthew B. Leaf, David A. McGinnis, Kathleen A. Oursler, Krisann K. Rimland, David Rodriguez-Barradas, Maria C. Sico, Jason J. Warner, Alberta L. Hsue, Priscilla Y. Kuller, Lewis H. Justice, Amy C. Freiberg, Matthew S. CA VACS Project Team TI Prehypertension, Hypertension, and the Risk of Acute Myocardial Infarction in HIV-Infected and -Uninfected Veterans SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE blood pressure; prehypertension; HIV; myocardial infarction ID ACTIVE ANTIRETROVIRAL THERAPY; INTIMA-MEDIA THICKNESS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; LARGE COHORT; PREVALENCE; ATHEROSCLEROSIS; ASSOCIATION; PROGRESSION; DATABASE AB Background. Compared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status. Methods. The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1: 2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression. Results. Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07-2.39]; HR, 1.81 [95% CI, 1.22-2.68]; HR, 2.57 [95% CI, 1.76-3.76]; and HR, 2.76 [95% CI, 1.90-4.02], respectively). Conclusions. HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk. C1 [Armah, Kaku A.; Chang, Chung-Chou H.; Kuller, Lewis H.; Freiberg, Matthew S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Chang, Chung-Chou H.; Freiberg, Matthew S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Baker, Jason V.] Univ Minnesota, Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA. [Ramachandran, Vasan S.] Boston Univ Sch Med, Cardiol Sect, Framingham Heart Study, Boston, MA USA. [Ramachandran, Vasan S.] Boston Univ Sch Med, Dept Prevent Med & Epidemiol, Boston, MA USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Budoff, Matthew J.] Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Crane, Heidi M.] Univ Washington Sch Med, Seattle, WA USA. [Gibert, Cynthia L.] Vet Affairs VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ Med Ctr, Washington, DC USA. [Goetz, Matthew B.; Leaf, David A.; Warner, Alberta L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew B.; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Oursler, Krisann K.] Univ Maryland Sch Med, Baltimore VA Med Ctr, Baltimore, MD USA. [Rimland, David] Emory Univ Sch Med, VA Med Ctr, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Sico, Jason J.; Justice, Amy C.] Yale Univ Sch Med, West Haven Vet Adm Med Ctr, VA Connecticut Hlth Care Syst, New Haven, CT USA. [Hsue, Priscilla Y.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. RP Freiberg, MS (reprint author), Univ Pittsburgh Sch Med, 230 McKee Pl,Suite 623, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu OI Goetz, Matthew/0000-0003-4542-992X FU National Heart, Lung, and Blood Institute; National Institute on Alcohol Abuse and Alcoholism at the NIH [HL095136-04, AA013566-10, AA020790, AA020794] FX This work was supported by the National Heart, Lung, and Blood Institute and the National Institute on Alcohol Abuse and Alcoholism at the NIH (grant numbers HL095136-04 to M. S. F. and A. C. J., and AA013566-10, AA020790, and AA020794 to A. C. J.). NR 32 TC 18 Z9 18 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2014 VL 58 IS 1 BP 121 EP 129 DI 10.1093/cid/cit652 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 280QC UT WOS:000329044800027 PM 24065316 ER PT J AU Longenecker, CT Triant, VA AF Longenecker, Chris T. Triant, Virginia A. TI Initiation of antiretroviral therapy at high CD4 cell counts: does it reduce the risk of cardiovascular disease? SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE antiretroviral therapy; cardiovascular disease; heart failure; immune activation; sudden cardiac death ID HIV-INFECTED PATIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; INTIMA-MEDIA THICKNESS; ACUTE MYOCARDIAL-INFARCTION; REVERSE-TRANSCRIPTASE INHIBITORS; CAROTID-ARTERY-DISEASE; CORONARY-HEART-DISEASE; HEALTH-CARE-SYSTEM; NON-AIDS EVENTS; ENDOTHELIAL FUNCTION AB Purpose of reviewInflammation and immune activation associated with untreated HIV infection may increase the risk for cardiovascular disease (CVD) and are not entirely reversed by antiretroviral therapy (ART). Although older ART regimens were associated with drug-specific risks for CVD, this may not be true for modern ART. Thus, with regard to CVD risk, the net benefit of initiating ART at higher CD4(+) T-cell counts remains unclear.Recent findingsIn addition to the well established risk of coronary heart disease, emerging evidence now suggests that chronic HIV infection is associated with higher risk of ischemic stroke, heart failure, and arrhythmias. These epidemiologic studies have associated immunodeficiency and active viral replication with higher CVD risk. Novel methods of imaging subclinical vascular disease continue to implicate inflammation and immune activation as likely mediators of CVD among patients with HIV. Newer generation protease inhibitors, chemokine receptor 5 antagonists, and integrase inhibitors do not appear to be associated with the adverse cardiometabolic risks of older drugs.SummaryRecent evidence suggests that treating HIV infection with ART may reduce the risk of CVD, even at higher CD4 T-cell counts; however, the definitive answer to this question will come from clinical trials and long-term observational studies. C1 [Longenecker, Chris T.] Univ Hosp Harrington Heart & Vasc Inst, Cleveland, OH USA. [Longenecker, Chris T.] Case Western Reserve Univ Sch Med, Cleveland, OH 44106 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Longenecker, CT (reprint author), Case Western Reserve Univ Sch Med, Univ Hosp Harrington Heart & Vasc Inst, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM chris.longenecker@uhhospitals.org FU National Institutes of Health [U01AI105937]; Medtronic Foundation; Bristol-Myers Squibb; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [K01AI073109] FX C.T.L. is supported by a grant from the National Institutes of Health (U01AI105937) and a grant from the Medtronic Foundation. He has received additional research funding from Bristol-Myers Squibb. V. A. T. is supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (K01AI073109). NR 107 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2014 VL 9 IS 1 BP 54 EP 62 DI 10.1097/COH.0000000000000015 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 282PW UT WOS:000329185500009 PM 24275676 ER PT J AU Marini, RP Cassiday, PK Venezia, J Shen, Z Buckley, EM Peters, Y Taylor, N Dewhirst, FE Tondella, ML Fox, JG AF Marini, Robert P. Cassiday, Pamela K. Venezia, Jaime Shen, Zeli Buckley, Ellen M. Peters, Yaicha Taylor, Nancy Dewhirst, Floyd E. Tondella, Maria L. Fox, James G. TI Corynebacterium ulcerans in Ferrets SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID DIPHTHERIAE; MACAQUES; CAT C1 [Marini, Robert P.; Venezia, Jaime; Shen, Zeli; Buckley, Ellen M.; Peters, Yaicha; Taylor, Nancy; Fox, James G.] MIT, Cambridge, MA 02139 USA. [Cassiday, Pamela K.; Tondella, Maria L.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Dewhirst, Floyd E.] Forsyth Inst, Cambridge, MA USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Bldg 16-825C,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NIEHS NIH HHS [P30 ES002109]; NIH HHS [T32 OD010978] NR 10 TC 7 Z9 7 U1 1 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2014 VL 20 IS 1 BP 159 EP 161 DI 10.3201/eid2001.130675 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 283UI UT WOS:000329272100032 PM 24377676 ER PT J AU O'Brien, J Jackson, JW Grodstein, F Blacker, D Weuve, J AF O'Brien, Jacqueline Jackson, John W. Grodstein, Francine Blacker, Deborah Weuve, Jennifer TI Postmenopausal Hormone Therapy Is Not Associated With Risk of All-Cause Dementia and Alzheimers Disease SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE Alzheimer disease; clinical trial; cognition; cohort studies; dementia; estrogen replacement therapy; hormone replacement therapy; systematic review ID ESTROGEN-REPLACEMENT THERAPY; HEALTH INITIATIVE MEMORY; CONJUGATED EQUINE ESTROGENS; MILD COGNITIVE IMPAIRMENT; SERVICES-TASK-FORCE; RANDOMIZED CONTROLLED-TRIAL; WOMENS HEALTH; CLINICAL-TRIALS; PLUS PROGESTIN; CACHE COUNTY AB The relationship of postmenopausal hormone therapy with all-cause dementia and Alzheimers disease dementia has been controversial. Given continued interest in the role of hormone therapy in chronic disease prevention and the emergence of more prospective studies, we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on postmenopausal hormone therapy use and risk of Alzheimers disease or dementia. A systematic search of Medline and Embase through December 31, 2012, returned 15 articles meeting our criteria. Our meta-analysis of any versus never use did not support the hypothesis that hormone therapy reduces risk of Alzheimers disease (summary estimate 0.88, 95 confidence interval: 0.66, 1.16). Exclusion of trial findings did not change this estimate. There were not enough all-cause dementia results for a separate meta-analysis, but when we combined all-cause dementia results (n 3) with Alzheimers disease results (n 7), the summary estimate remained null (summary estimate 0.94, 95 confidence interval: 0.71, 1.26). The limited explorations of timing of useuboth duration and early initiationudid not yield consistent findings. Our findings support current recommendations that hormone therapy should not be used for dementia prevention. We discuss trends in hormone therapy research that could explain our novel findings and highlight areas where additional data are needed. C1 [O'Brien, Jacqueline; Jackson, John W.; Grodstein, Francine; Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [O'Brien, Jacqueline; Grodstein, Francine] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [O'Brien, Jacqueline] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA. [Jackson, John W.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Weuve, Jennifer] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Chicago, IL 60612 USA. [Weuve, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP O'Brien, J (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jlo391@mail.harvard.edu FU National Institutes of Health/National Institute of Environmental Health Sciences [T32-AG000158, T32-MH017119, R21ES020404]; Alzheimer's Association [NIRG 242395]; Horace W. Goldsmith Fellowship at Harvard University FX This work was supported by the National Institutes of Health/National Institute of Environmental Health Sciences (T32-AG000158 (J. O.), T32-MH017119 (J. W. J.), R21ES020404 (J. W.)); the Alzheimer's Association (NIRG 242395 (J. W.)); the Horace W. Goldsmith Fellowship at Harvard University (J. W. J.); and a grant from an anonymous foundation (D. B.). NR 76 TC 20 Z9 20 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2014 VL 36 IS 1 SI SI BP 83 EP 103 DI 10.1093/epirev/mxt008 PG 21 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 281WK UT WOS:000329131500008 PM 24042430 ER PT J AU Floyd, LM Holmes, TC Dean, JC AF Floyd, Lisa M. Holmes, Taylor C. Dean, Jesse C. TI Reduced effects of tendon vibration with increased task demand during active, cyclical ankle movements SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Motor control; Movement accuracy; Proprioception; Tendon vibration ID MUSCLE VIBRATION; POSITION SENSE; DIABETIC-NEUROPATHY; AFFERENTS; CONTRACTION; RESPONSES; SPINDLES; HUMANS; STANCE; INFORMATION AB Tendon vibration can alter proprioceptive feedback, one source of sensory information which humans can use to produce accurate movements. However, the effects of tendon vibration during functional movement vary depending on the task. For example, ankle tendon vibration has considerably smaller effects during walking than standing posture. The purpose of this study was to test whether the effects of ankle tendon vibration are predictably influenced by the mechanical demands of a task, as quantified by peak velocity. Twelve participants performed symmetric, cyclical ankle plantar flexion/dorsiflexion movements while lying prone with their ankle motion unconstrained. The prescribed movement period (1, 3 s) and peak-to-peak amplitude (10A degrees, 15A degrees, 20A degrees) were varied across trials; shorter movement periods or larger amplitudes increased the peak velocity. In some trials, vibration was continuously and simultaneously applied to the right ankle plantar flexor and dorsiflexor tendons, while the left ankle tendons were never vibrated. The vibration frequency (40, 80, 120, 160 Hz) was varied across trials. During trials without vibration, participants accurately matched the movement of their ankles. The application of 80 Hz vibration to the right ankle tendons significantly reduced the amplitude of right ankle movement. However, the effect of vibration was smaller during more mechanically demanding (i.e., higher peak velocity) movements. Higher vibration frequencies had larger effects on movement accuracy, possibly due to parallel increases in vibration amplitude. These results demonstrate that the effects of ankle tendon vibration are dependent on the mechanical demand of the task being performed, but cannot definitively identify the underlying physiological mechanism. C1 [Floyd, Lisa M.; Holmes, Taylor C.; Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Dean, JC (reprint author), Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, 77 President St,MSC700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU Department of Veterans Affairs [1IK2RX000750] FX This study was partially funded by a grant from the Department of Veterans Affairs, number 1IK2RX000750. NR 48 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 EI 1432-1106 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2014 VL 232 IS 1 BP 283 EP 292 DI 10.1007/s00221-013-3739-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 283GE UT WOS:000329233400025 PM 24136344 ER PT J AU Scheuner, MT Hamilton, AB Peredo, J Sale, TJ Austin, C Gilman, SC Bowen, MS Goldzweig, CL Lee, M Mittman, BS Yano, EM AF Scheuner, Maren T. Hamilton, Alison B. Peredo, Jane Sale, Taylor J. Austin, Colletta Gilman, Stuart C. Bowen, M. Scott Goldzweig, Caroline Lubick Lee, Martin Mittman, Brian S. Yano, Elizabeth M. TI A cancer genetics toolkit improves access to genetic services through documentation and use of the family history by primary-care clinicians SO GENETICS IN MEDICINE LA English DT Article DE family history; hereditary cancer; referral ID BRCA2 MUTATION CARRIERS; CONTINUING MEDICAL-EDUCATION; WOMENS HEALTH-CARE; BREAST-CANCER; COLORECTAL-CANCER; LYNCH-SYNDROME; GENOMIC MEDICINE; RISK-ASSESSMENT; OVARIAN-CANCER; DELIVERY AB Purpose: We developed, implemented, and evaluated a multicomponent cancer genetics toolkit designed to improve recognition and appropriate referral of individuals at risk for hereditary cancer syndromes. Methods: We evaluated toolkit implementation in the women's clinics at a large Veterans Administration medical center using mixed methods, including pre-post semistructured interviews, clinician surveys, and chart reviews, and during implementation, monthly tracking of genetic consultation requests and use of a reminder in the electronic health record. We randomly sampled 10% of progress notes 6 months before (n = 139) and 18 months during implementation (n = 677). Results: The toolkit increased cancer family history documentation by almost 10% (26.6% pre- and 36.3% postimplementation). The reminder was a key component of the toolkit; when used, it was associated with a twofold increase in cancer family history documentation (odds ratio = 2.09; 95% confidence interval: 1.39-3.15), and the history was more complete. Patients whose clinicians completed the reminder were twice as likely to be referred for genetic consultation (4.1-9.6%, P < 0.0001). Conclusion: A multicomponent approach to the systematic collection and use of family history by primary-care clinicians increased access to genetic services. C1 [Scheuner, Maren T.; Hamilton, Alison B.; Peredo, Jane; Sale, Taylor J.; Austin, Colletta; Goldzweig, Caroline Lubick; Lee, Martin; Mittman, Brian S.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Scheuner, Maren T.; Goldzweig, Caroline Lubick] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Gilman, Stuart C.] Vet Hlth Adm, Off Acad Affiliat, Washington, DC USA. [Bowen, M. Scott] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Lee, Martin; Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Scheuner, MT (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM maren.scheuner@va.gov OI Mittman, Brian/0000-0003-3589-9178 FU Centers for Disease Control and Prevention [1U38GD000047] FX This publication was supported by Cooperative Agreement No. 1U38GD000047 from the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention. We thank Muin Khoury for his review of the manuscript (he received no compensation), Lisa V. Rubenstein for her input to the study design and review of implementation activities, Shannon Rhodes for data management and preliminary analyses, and Austin Jones for his contributions to data entry and quality assurance. Rubenstein, Rhodes, and Jones provided these services in their respective roles as employees at the VA Greater Los Angeles Healthcare System. NR 38 TC 11 Z9 11 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JAN PY 2014 VL 16 IS 1 BP 60 EP 69 DI 10.1038/gim.2013.75 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 284GO UT WOS:000329304300009 PM 23765051 ER PT B AU Schorge, JO Chi, DS AF Schorge, John O. Chi, Dennis S. BE Odunsi, K Pejovic, T TI Surgical Management of Ovarian Cancer SO GYNECOLOGIC CANCERS: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT SE Current Multidisciplinary Oncology LA English DT Article; Book Chapter ID PRIMARY CYTOREDUCTIVE SURGERY; ADVANCED-STAGE OVARIAN; RECURRENT EPITHELIAL OVARIAN; INTERVAL DEBULKING SURGERY; PRIMARY PERITONEAL CANCERS; GYNECOLOGIC-ONCOLOGY-GROUP; NEOADJUVANT CHEMOTHERAPY; BOWEL OBSTRUCTION; FALLOPIAN-TUBE; TERTIARY CYTOREDUCTION C1 [Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02115 USA. [Chi, Dennis S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Schorge, JO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02115 USA. NR 80 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-89-5 J9 CURR MULTIDISC ONCOL PY 2014 BP 115 EP 125 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BIF33 UT WOS:000328003400015 ER PT B AU Bradford, L Ambrosio, A Birrer, MJ AF Bradford, Leslie Ambrosio, Allison Birrer, Michael J. BE Odunsi, K Pejovic, T TI PARP Inhibitors in Gynecologic Malignancies SO GYNECOLOGIC CANCERS: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT SE Current Multidisciplinary Oncology LA English DT Article; Book Chapter ID EPITHELIAL OVARIAN-CANCER; BRCA2 MUTATIONS; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; SOMATIC MUTATIONS; BREAST-CANCER; MUTANT-CELLS; DNA-DAMAGE; CISPLATIN; TUMORS C1 [Bradford, Leslie; Ambrosio, Allison] Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. [Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Dept Hematol Oncol, Boston, MA USA. RP Bradford, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-89-5 J9 CURR MULTIDISC ONCOL PY 2014 BP 231 EP 239 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BIF33 UT WOS:000328003400028 ER PT J AU Sherman, KE Thomas, D Chung, RT AF Sherman, Kenneth E. Thomas, David Chung, Raymond T. TI Human Immunodeficiency Virus and Liver Disease Forum 2012 SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; HIV-INFECTED PATIENTS; NONCIRRHOTIC PORTAL-HYPERTENSION; SUSTAINED VIROLOGICAL RESPONSE; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; DRUG-USERS; TRANSPLANT RECIPIENTS; PEGYLATED INTERFERON; COINFECTION AB In the United States, more than 1.1 million individuals are infected with the human immunodeficiency virus (HIV). These patients exhibit a high frequency of coinfections with other hepatotropic viruses and ongoing fibrosis, leading to cirrhosis and liver-related mortality. Etiologies of liver disease include viral hepatitis coinfections, drug-related hepatotoxicity, fatty liver disease, and direct and indirect effects from HIV infection, including increased bacterial translocation, immune activation, and presence of soluble proteins, that modulate the hepatic cytokine environment. New treatments for hepatitis C virus (HCV) using direct-acting agents appear viable, though issues related to intrinsic toxicities and drug-drug interactions remain. Recent research suggests that acute HCV infection, unrecognized hepatitis D infection, and hepatitis E may all represent emergent areas of concern. Antiretroviral agents, including those used in recent years, may represent risk factors for hepatic injury and portal hypertension. Key issues in the future include systematic implementation of liver disease management and new treatment in HIV-infected populations with concomitant injection drug use, alcohol use, and low socioeconomic status. (Hepatology 2014;58:307-317) C1 [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. [Thomas, David] Johns Hopkins Med Inst, Div Infect Dis, Baltimore, MD 21205 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, 231 Albert Sabin Way,ML 0595, Cincinnati, OH 45267 USA. EM shermake@ucmail.uc.edu FU National Institutes of Health (from the National Institute of Allergy and Infectious Diseases) [R13AI071925]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Merck; Genentech; Bristol-Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc. FX Funding for this conference was made possible, in part, by the National Institutes of Health (under award no. R13AI071925 from the National Institute of Allergy and Infectious Diseases), with cofunding from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. This work was supported by educational grants from Merck, Genentech, Bristol-Myers Squibb, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. administered by Janssen Services, LLC, and Kadmon Pharmaceuticals, LLC. NR 61 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JAN PY 2014 VL 59 IS 1 BP 307 EP 317 DI 10.1002/hep.26638 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 276GZ UT WOS:000328738400032 PM 23904401 ER PT J AU Ozel, AB Moroi, SE Reed, DM Nika, M Schmidt, CM Akbari, S Scott, K Rozsa, F Pawar, H Musch, DC Lichter, PR Gaasterland, D Branham, K Gilbert, J Garnai, SJ Chen, W Othman, M Heckenlively, J Swaroop, A Abecasis, G Friedman, DS Zack, D Ashley-Koch, A Ulmer, M Kang, JH Liu, YT Yaspan, BL Haines, J Allingham, RR Hauser, MA Pasquale, L Wiggs, J Richards, JE Li, JZ AF Ozel, A. Bilge Moroi, Sayoko E. Reed, David M. Nika, Melisa Schmidt, Caroline M. Akbari, Sara Scott, Kathleen Rozsa, Frank Pawar, Hemant Musch, David C. Lichter, Paul R. Gaasterland, Doug Branham, Kari Gilbert, Jesse Garnai, Sarah J. Chen, Wei Othman, Mohammad Heckenlively, John Swaroop, Anand Abecasis, Goncalo Friedman, David S. Zack, Don Ashley-Koch, Allison Ulmer, Megan Kang, Jae H. Liu, Yutao Yaspan, Brian L. Haines, Jonathan Allingham, R. Rand Hauser, Michael A. Pasquale, Louis Wiggs, Janey Richards, Julia E. Li, Jun Z. CA NEIGHBOR Consortium TI Genome-wide association study and meta-analysis of intraocular pressure SO HUMAN GENETICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; CENTRAL CORNEAL THICKNESS; TO-DISC RATIO; MACULAR DEGENERATION; MOLECULAR-BIOLOGY; GENETIC-VARIANTS; RISK-FACTORS; HERITABILITY; EYE; POPULATION AB Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in > 6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 x 10(-8)). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk. C1 [Ozel, A. Bilge; Li, Jun Z.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Moroi, Sayoko E.; Reed, David M.; Nika, Melisa; Schmidt, Caroline M.; Akbari, Sara; Scott, Kathleen; Rozsa, Frank; Pawar, Hemant; Musch, David C.; Lichter, Paul R.; Branham, Kari; Gilbert, Jesse; Garnai, Sarah J.; Othman, Mohammad; Heckenlively, John; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Musch, David C.; Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Gaasterland, Doug] Eye Doctors Washington DC, Washington, DC USA. [Chen, Wei] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Div Pulm Med Allergy & Immunol, Pittsburgh, PA USA. [Chen, Wei] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Chen, Wei] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA. [Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Friedman, David S.; Zack, Don] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Ashley-Koch, Allison; Ulmer, Megan; Liu, Yutao; Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Sch Med, Ctr Human Genet, Durham, NC USA. [Kang, Jae H.; Pasquale, Louis] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Yaspan, Brian L.; Haines, Jonathan] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Pasquale, Louis; Wiggs, Janey] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Li, JZ (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. EM smoroi@med.umich.edu; junzli@med.umich.edu OI Rozsa, Frank/0000-0002-1378-7020; Reed, David/0000-0002-4772-6138; Carnes, Megan/0000-0002-7270-132X; Zack, Don/0000-0002-7966-1973; Swaroop, Anand/0000-0002-1975-1141; Ashley-Koch, Allison/0000-0001-5409-9155 FU University of Michigan Glaucoma Research Center; Ellison Medical Foundation; Harvard Glaucoma Center for Excellence; Margolis Fund; Research to Prevent Blindness; Glaucoma Research Foundation; Glaucoma Foundation; American Health Assistance Foundation; Elmer and Silvia Sramek Foundation; Foundation Fighting Blindness; Macula Vision Research Foundation; Pew Charitable Trusts; Casey Macular Degeneration Center Fund; Marion W. and Edward F. Knight AMD Fund; Harold and Pauline Price Foundation; National Genotyping Centre of Spain FX Other supports included funding from University of Michigan Glaucoma Research Center (S. E. M., J.E.R., J.Z.L.); Ellison Medical Foundation (J.Z.L.); Harvard Glaucoma Center for Excellence, and the Margolis Fund (J.W. and L. P.); Research to Prevent Blindness (A. S., D. C. M., J.W., L. P., J.R.H., and J.E.R.); the Glaucoma Research Foundation (S. E. M., Y.L.); the Glaucoma Foundation (Y.L.); American Health Assistance Foundation (Y.L., J.E.R., J.R.H., A. S.); Elmer and Silvia Sramek Foundation (J.R.H., A. S.); Foundation Fighting Blindness (J.R.H., A. S.); the Macula Vision Research Foundation (J.R.H., A. S.); the Pew Charitable Trusts (J.R.H., A. S.); the Casey Macular Degeneration Center Fund (J.R.H., A. S.); the Marion W. and Edward F. Knight AMD Fund (J.R.H., A. S.); the Harold and Pauline Price Foundation, National Genotyping Centre of Spain (J.R.H., A.S.). NR 50 TC 30 Z9 30 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD JAN PY 2014 VL 133 IS 1 BP 41 EP 57 DI 10.1007/s00439-013-1349-5 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 283KH UT WOS:000329244500004 PM 24002674 ER PT J AU Adappa, ND Zhang, Z Palmer, JN Kennedy, DW Doghramji, L Lysenko, A Reed, DR Scott, T Zhao, NW Owens, D Lee, RJ Cohen, NA AF Adappa, Nithin D. Zhang, Zi Palmer, James N. Kennedy, David W. Doghramji, Laurel Lysenko, Anna Reed, Danielle R. Scott, Thomas Zhao, Nina W. Owens, David Lee, Robert J. Cohen, Noam A. TI The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE innate immunity; antimicrobial; nitric oxide; mucociliary clearance; endoscopic sinus surgery; genetics ID SOLITARY CHEMOSENSORY CELLS; STAPHYLOCOCCUS-AUREUS; INNATE IMMUNITY; NASAL POLYPS; EXPRESSION; GENETICS; BIOFILMS; DISEASE; PATHOGENESIS; RESPONSES AB BackgroundThe bitter taste receptor T2R38 was recently described to play a role in upper airway innate mucosal defense. When activated by bacterial quorum-sensing molecules, T2R38 stimulates the ciliated epithelial cells to produce nitric oxide (NO), resulting in bactericidal activity and an increase in mucociliary clearance (MCC). Polymorphisms within the T2R38 gene (TAS2R38) confer variability in activation of the receptor yielding dramatic differences in upper airway defensive responses (NO production and accelerated MCC) to microbial stimulation based on genotype. Our objective was to determine whether the nonprotective TAS2R38 polymorphisms, which render the receptor inactive, correlate with medically recalcitrant chronic rhinosinusitis (CRS) necessitating surgical intervention in the context of known risk factors, and thus identify whether the TAS2R38 genotype is an independent risk factor for patients undergoing functional endoscopic sinus surgery (FESS). MethodsCRS patients undergoing primary FESS were prospectively genotyped for TAS2R38. Chi-square analysis was performed on the genotype distribution with respect to other risk factors, including allergies, asthma, nasal polyposis, aspirin sensitivity, diabetes, and smoking exposure. ResultsSeventy primary FESS patients were genotyped demonstrating a statistically significant skewing from the expected distribution of the general population (p < 0.0383). CRS patients with a particular polymorphism seemed less likely to have allergies, asthma, nasal polyposis, aspirin sensitivity, and diabetes, but this did not demonstrate statistical significance. ConclusionOur investigation suggests that TAS2R38 genotype is an independent risk factor for patients failing medical therapy, necessitating surgical intervention. (C) 2013 ARS-AAOA, LLC. C1 [Adappa, Nithin D.; Zhang, Zi; Palmer, James N.; Kennedy, David W.; Doghramji, Laurel; Scott, Thomas; Zhao, Nina W.; Owens, David; Lee, Robert J.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Lysenko, Anna; Reed, Danielle R.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Adappa, ND (reprint author), Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM Nithin.Adappa@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Reed, Danielle/0000-0002-4374-6107; Lee, Robert/0000-0001-5826-6686 FU NIDCD NIH HHS [P30 DC011735] NR 34 TC 39 Z9 39 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JAN PY 2014 VL 4 IS 1 BP 3 EP 7 DI 10.1002/alr.21253 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 282EF UT WOS:000329152400002 PM 24302675 ER PT J AU Chung, D Park, KT Yarlagadda, B Davis, EM Platt, M AF Chung, Daniel Park, K. T. Yarlagadda, Bharat Davis, Elizabeth Mahoney Platt, Michael TI The significance of serum total immunoglobulin E for in vitro diagnosis of allergic rhinitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE allergic rhinitis; immunoglobulin E; in vitro testing; atopy; allergy ID SKIN-TEST REACTIVITY; REFERENCE VALUES; IGE LEVELS; POPULATION; SENSITIZATION; ASSOCIATION; PREVALENCE; CHILDREN; ADULTS AB BackgroundAllergic rhinitis is diagnosed by clinical parameters with no widely accepted screening test. Measurement of total serum immunoglobulin E (IgE) has limited use in the general population due to a low negative predictive value. The value of total IgE level in select populations undergoing in vitro allergy testing remains unknown. The aim of this study is to determine the utility of total serum IgE in the in vitro diagnosis of allergic rhinitis. MethodsA retrospective chart review of patients undergoing testing for allergic rhinitis was performed. Clinical parameters, total IgE level, and enzyme-linked immunosorbent assay (ELISA) for serum-specific IgE levels were analyzed with multivariate logistic regression. The positive and negative predictive values and a receiver operating characteristic (ROC) curve were used to assess the utility of total IgE in predicting serum-specific IgE test results. ResultsRecords from 1073 patients were reviewed. ROC curve for total IgE >150 IU/mL (sigma 0.88) indicates good discrimination in identifying patients with sensitization by in vitro testing, whereas low total IgE level had strong negative predictive value (0.87, IgE <10) in identifying negative specific IgE testing. Multivariate logistic regression showed that differences in covariables did not significantly change the odds of a positive in vitro allergy test panel. ConclusionSerum total IgE level is useful in the in vitro diagnosis of allergic rhinitis. In vitro testing for specific IgE may be unnecessary in patients with low serum total IgE, whereas high total IgE level suggests that in vitro testing would confirm specific sensitizations in patients with allergic rhinitis. (C) 2013 ARS-AAOA, LLC. C1 [Chung, Daniel; Davis, Elizabeth Mahoney; Platt, Michael] Boston Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. [Park, K. T.] Stanford Univ, Div Gastroenterol, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Yarlagadda, Bharat] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Platt, M (reprint author), Dept Otolaryngol Head & Neck Surg, 820 Harrison Ave,4th Floor, Boston, MA 02118 USA. EM miplatt@bu.edu NR 18 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JAN PY 2014 VL 4 IS 1 BP 56 EP 60 DI 10.1002/alr.21240 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 282EF UT WOS:000329152400011 PM 24227797 ER PT J AU Bleier, BS Lefebvre, DR Freitag, SK AF Bleier, Benjamin S. Lefebvre, Daniel R. Freitag, Suzanne K. TI Endoscopic orbital floor decompression with preservation of the inferomedial strut SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE orbital decompression; diplopia; inferomedial orbital strut; endoscopic orbital floor decompression ID SURGICAL DECOMPRESSION; DYSTHYROID ORBITOPATHY; DISEASE; DIPLOPIA AB BackgroundMedial and inferior orbital decompression is most commonly performed in the setting of dysthyroid orbitopathy. Diplopia represents the most common complication and may be minimized through the preservation of a bony inferomedial strut (IMS). Historically, this has required a transconjunctival approach due to the technical demands of performing an isolated orbital floor decompression using endoscopic instrumentation. Here we describe a novel technique of a purely endoscopic orbital floor decompression with reliable preservation of the IMS. MethodsDescription of a novel surgical technique for endoscopic orbital floor decompression with IMS preservation using frontal sinus instrumentation visualized by a 70-degree endoscope. ResultsWe have successfully used this technique in 12 orbits with 100% preservation of the bony inferomedial strut and no complications. The extent of decompression and width of the residual strut may be fine tuned as needed to optimize results. ConclusionOrbital floor decompression with IMS preservation may be reliably performed using purely endoscopic techniques. Successful completion of this procedure requires the adaptation of standard frontal sinus instrumentation to the maxillary sinus roof and thus may be readily mastered by any endoscopic surgeon comfortable with frontal sinus techniques. (C) 2013 ARS-AAOA, LLC. C1 [Bleier, Benjamin S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Lefebvre, Daniel R.; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Bleier, BS (reprint author), 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu NR 12 TC 5 Z9 5 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JAN PY 2014 VL 4 IS 1 BP 82 EP 84 DI 10.1002/alr.21231 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 282EF UT WOS:000329152400015 PM 24124099 ER PT J AU Gans, JS AF Gans, Jerome S. TI What an Understanding of the Dynamics of Gossip Has to Teach About Group Dynamics and Group Leadership SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article AB Although what transpires in group therapy is not gossip per se except perhaps when absent or former members are discussed listening to group interaction through an understanding of the dynamics of gossip can contribute to a greater appreciation of group dynamics and group leadership as well as enlarge therapeutic space. After examining the interpersonal dynamics of gossip, this paper discusses six ways in which an understanding of these dynamics can inform group leadership and shed light on group psychotherapy. Central features of gossip that appear in group interactions are explored: These include projection, displacement, self-esteem regulation, clarification of motivation, unself-consciousness, social comparison and bonding, avoidance of psychic pain, and making the ego-syntonic dystonic. The lively use of imagination in the mature phase of group therapy is conceived of as the time when the darker side of human nature imagined gossip harnessed for therapeutic purposes can be welcomed in and processed in a kind, playful, and compassionate manner. C1 [Gans, Jerome S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gans, Jerome S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02481 USA. EM Jsgans@comcast.net NR 19 TC 0 Z9 0 U1 1 U2 8 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 EI 1943-2836 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JAN PY 2014 VL 64 IS 1 BP 5 EP 22 PG 18 WC Psychology, Clinical SC Psychology GA 286NE UT WOS:000329475200002 ER PT J AU Dempsey, JA Xie, AL Patz, DS Wang, D AF Dempsey, Jerome A. Xie, Ailiang Patz, David S. Wang, David TI Physiology in Medicine: Obstructive sleep apnea pathogenesis and treatment-considerations beyond airway anatomy SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE chemosensitivity; collapsible airway; sleep apnea ID GENIOGLOSSAL MUSCLE-ACTIVITY; CHRONIC INTERMITTENT HYPOXIA; CHEYNE-STOKES RESPIRATION; HEART-FAILURE; NREM SLEEP; CAROTID-BODY; REM-SLEEP; LOOP GAIN; PULMONARY RESISTANCE; VENTILATORY CONTROL AB We review evidence in support of significant contributions to the pathogenesis of obstructive sleep apnea (OSA) from pathophysiological factors beyond the well-accepted importance of airway anatomy. Emphasis is placed on contributions from neurochemical control of central respiratory motor output through its effects on output stability, upper airway dilator muscle activation, and arousability. In turn, we consider the evidence demonstrating effective treatment of OSA via approaches that address each of these pathophysiologic risk factors. Finally, a case is made for combining treatments aimed at both anatomical and ventilatory control system deficiencies and for individualizing treatment to address a patient's own specific risk factors. C1 [Dempsey, Jerome A.; Xie, Ailiang] Univ Wisconsin, James B Skatrud Lab Pulm & Sleep Med, Middleton Vet Adm Hosp, Madison, WI 53706 USA. [Dempsey, Jerome A.; Xie, Ailiang] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. [Patz, David S.] St Marys Hosp, Dept Med, Grand Junction, CO USA. [Wang, David] Univ Sydney, Woolcock Inst Med Res, Camperdown, NSW, Australia. [Wang, David] Royal Prince Alfred Hosp, Dept Resp & Sleep Med, Camperdown, NSW 2050, Australia. RP Dempsey, JA (reprint author), Univ Wisconsin, 1300 Univ Ave,Rm 4245 MSC, Madison, WI 53706 USA. EM jdempsey@wisc.edu FU National Heart, Lung, and Blood Institute [HL-099724, HL-15469]; Veterans Administration Merit Review FX J. Dempsey and A. Xie were supported by National Heart, Lung, and Blood Institute Grants IIL-099724 and IIL-15469, and by a Veterans Administration Merit Review. NR 95 TC 17 Z9 17 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2014 VL 116 IS 1 BP 3 EP 12 DI 10.1152/japplphysiol.01054.2013 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 282TI UT WOS:000329196100002 PM 24201709 ER PT J AU Watada, S Yu, YM Fischman, AJ Kurihara, T Shen, CA Tompkins, RG Fagan, S AF Watada, Susumu Yu, Yong-Ming Fischman, Alan J. Kurihara, Tomohiro Shen, Chuan-an Tompkins, Ronald G. Fagan, Shawn TI Evaluation of Intragastric Vs Intraperitoneal Glucose Tolerance Tests in the Evaluation of Insulin Resistance in a Rodent Model of Burn Injury and Glucagon-Like Polypeptide-1 Treatment SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CRITICALLY-ILL PATIENTS; BETA-CELL FUNCTION; PEPTIDE-1; HYPOGLYCEMIA; METABOLISM; SECRETION; THERAPY; SENSITIVITY; IMPAIRMENT; EXTRACTION AB Evaluation of glucose tolerance in rodent models is usually performed after intraperitroneal administration of glucose (intraperitoneal glucose tolerance test [IPGTT]), whereas in humans the test is performed with oral glucose. Hyperglycemia is a major clinical manifestation of burn injury. Our previous studies using IPGTT have demonstrated burn injury-induced insulin resistance and the beneficial effects of glucagon-like polypeptide-1 (GLP-1) in improving insulin resistance. The goal of the present study is to compare the results of these two procedures under 1) burn injury-induced insulin resistance and 2) GLP-1 treatment after burn. Male CD rats were divided into three groups: sham burn, burn, and burn with GLP-1. Blood glucose and plasma insulin levels were measured during intragastric glucose tolerance test (IGGTT) on day 6 after 40% of full-thickness burn injury. The results were compared with our previous IPGTT. Blood glucose curves for IGGTT and IPGTT showed a similar pattern. However, IGGTT demonstrated a significant lower level of maximal blood glucose when compared with IPGTT. This was accompanied by higher peak insulin levels in sham burn and burn groups. In contrast, peak insulin levels of each burn with GLP-1 group were similar. 1) Both IPGTT and IGGTT demonstrated burn injury-induced insulin resistance and the efficacy of GLP-1 for reducing hyperglycemia after burn injury. 2) The observed differences in the plasma glucose and insulin levels between IGGTT and IPGTT suggest that endogenously produced GLP-1 during the IGGTT may play a role in ameliorating insulin resistance after burn injury. C1 [Watada, Susumu; Yu, Yong-Ming; Kurihara, Tomohiro; Shen, Chuan-an; Tompkins, Ronald G.; Fagan, Shawn] Harvard Univ, Sch Med, Dept Surg, Burn Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Watada, Susumu; Yu, Yong-Ming; Fischman, Alan J.; Kurihara, Tomohiro; Shen, Chuan-an; Tompkins, Ronald G.; Fagan, Shawn] Shriners Hosp Children, Boston, MA 02114 USA. RP Yu, YM (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. FU National Institutes of Health [5P50GM021700, P30DK040561-13]; Shriners Hospitals for Children [84070, 85700] FX This study was supported by grants from the National Institutes of Health (5P50GM021700, P30DK040561-13) and Shriners Hospitals for Children (Grants 84070 and 85700). NR 29 TC 3 Z9 4 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2014 VL 35 IS 1 BP E66 EP E72 DI 10.1097/BCR.0b013e31828a8ede PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 284ED UT WOS:000329298000019 PM 23511296 ER PT J AU Weathington, NM Mallampalli, RK AF Weathington, Nathaniel M. Mallampalli, Rama K. TI Emerging therapies targeting the ubiquitin proteasome system in cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID NF-KAPPA-B; REFRACTORY MULTIPLE-MYELOMA; SINGLE-AGENT CARFILZOMIB; SMALL-MOLECULE INHIBITOR; OPEN-LABEL; DEUBIQUITINATING ENZYME; ALLOSTERIC INHIBITOR; CEREBLON EXPRESSION; BORTEZOMIB; APOPTOSIS AB The ubiquitin proteasome system (UPS) is an essential metabolic constituent of cellular physiology that tightly regulates cellular protein concentrations with specificity and precision to optimize cellular function. Inhibition of the proteasome has proven very effective in the treatment of multiple myeloma, and this approach is being tested for utility in other malignancies. New pharmaceuticals targeting the proteasome itself or specific proximal pathways of the UPS are in development as antiproliferatives or immunomodulatory agents. In this article, we discuss the biology of UPS-targeting drugs, their use as therapy for neoplasia, and the state of clinical and preclinical development for emerging therapeutics. C1 [Weathington, Nathaniel M.; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15213 USA. [Weathington, Nathaniel M.; Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, UPMC Montefiore, Dept Med, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; NIH R01 [HL096376, HL097376, HL098174]; NIH P01 [HL114453]; US Department of Veterans Affairs FX This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs, NIH R01 grants HL096376, HL097376, and HL098174, and NIH P01 grant HL114453 (to R.K. Mallampalli). NR 71 TC 36 Z9 39 U1 0 U2 22 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2014 VL 124 IS 1 BP 6 EP 12 DI 10.1172/JCI71602 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 284PX UT WOS:000329333500003 PM 24382383 ER PT J AU Adini, I Ghosh, K Adini, A Chi, ZL Yoshimura, T Benny, O Connor, KM Rogers, MS Bazinet, L Birsner, AE Bielenberg, DR D'Amato, RJ AF Adini, Irit Ghosh, Kaustabh Adini, Avner Chi, Zai-Long Yoshimura, Takeru Benny, Ofra Connor, Kip M. Rogers, Michael S. Bazinet, Lauren Birsner, Amy E. Bielenberg, Diane R. D'Amato, Robert J. TI Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MACULAR DEGENERATION; IN-VIVO; GROWTH-FACTOR; DIFFERENTIAL EXPRESSION; ENDOTHELIAL-CELLS; UVEAL MELANOMA; UNITED-STATES; MOUSE CORNEA; COLLAGEN; TYROSINASE AB Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases. C1 [Adini, Irit; Adini, Avner; Chi, Zai-Long; Yoshimura, Takeru; Benny, Ofra; Rogers, Michael S.; Bazinet, Lauren; Birsner, Amy E.; Bielenberg, Diane R.; D'Amato, Robert J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program,Dept Surg, Boston, MA 02115 USA. [Ghosh, Kaustabh] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA. [Connor, Kip M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA. [D'Amato, Robert J.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Adini, I (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program,Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM irit.adini@childrens.harvard.edu OI Connor, Kip/0000-0002-2048-9080 FU NIH [R01EY012726] FX We acknowledge Ake Oldberg for generously sharing Fmod-KO mice. We also thank Alexeev Y. Vitali for murine melanocyte cells. This study was supported in part by a grant from the NIH (R01EY012726). NR 46 TC 16 Z9 16 U1 1 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2014 VL 124 IS 1 BP 425 EP 436 DI 10.1172/JCI69404 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 284PX UT WOS:000329333500047 PM 24355922 ER PT J AU Fong, ZV Ferrone, CR Thayer, SP Wargo, JA Sahora, K Seefeld, KJ Warshaw, AL Lillemoe, KD Hutter, MM Fernandez-del Castillo, C AF Fong, Zhi Ven Ferrone, Cristina R. Thayer, Sarah P. Wargo, Jennifer A. Sahora, Klaus Seefeld, Kimberly J. Warshaw, Andrew L. Lillemoe, Keith D. Hutter, Mathew M. Fernandez-del Castillo, Carlos TI Understanding Hospital Readmissions After Pancreaticoduodenectomy: Can We Prevent Them? SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Hospital readmission; Pancreaticoduodenectomy; Quality metric ID INTERNATIONAL STUDY-GROUP; PANCREATIC RESECTION; MORTALITY; CANCER; DEFINITION; MANAGEMENT; SURGERY; QUALITY AB The morbidity and mortality of pancreaticoduodenectomy (PD) have significantly decreased over the past decades to the point that they are no longer the sole indicators of quality and safety. In recent times, hospital readmission is increasingly used as a quality metric for surgical performance and has direct implications on health-care costs. We sought to delineate the natural history and predictive factors of readmissions after PD. The clinicopathologic and long-term follow-up data of 1,173 consecutive patients who underwent PD between August 2002 and August 2012 at the Massachusetts General Hospital were reviewed. The NSQIP database was linked with our clinical database to supplement perioperative data. Readmissions unrelated to the index admission were omitted. We identified 173 (15 %) patients who required readmission after PD within the study period. The readmission rate was higher in the second half of the decade when compared to the first half (18.6 vs 12.3 %, p = 0.003), despite a stable 7-day median length of stay. Readmitted patients were analyzed against those without readmissions after PD. The demographics and tumor pathology of both groups did not differ significantly. In the multivariate logistic regression analysis, pancreatic fistula (18.5 vs 11.3 %, OR 1.86, p = 0.004), multivisceral resection at time of PD (3.5 vs 0.6 %, OR 4.02, p = 0.02), length of initial hospital stay > 7 days (59.5 vs 42.5 %, OR 1.57, p = 0.01), and ICU admissions (11.6 vs 3.4 %, OR 2.90, p = 0.0005) were independently associated with readmissions. There were no postoperative biochemical variables that were predictive of readmissions. Fifty percent (n = 87) of the readmissions occurred within 7 days from initial operative discharge. The reasons for immediate (a parts per thousand currency sign7 days) and nonimmediate (> 7 days) readmissions differed; ileus, delayed gastric emptying, and pneumonia were more common in early readmissions, whereas wound infection, failure to thrive, and intra-abdominal hemorrhage were associated with late readmissions. The incidences of readmissions due to pancreatic fistulas and intra-abdominal abscesses were equally distributed between both time frames. The frequency of readmission after PD is 15 % and has been on the uptrend over the last decade. The complexity of initial resection and pancreatic fistula were independently associated with hospital readmissions after PD. Further efforts should be centered on preventing early readmissions, which constitute half of all readmissions. C1 [Fong, Zhi Ven; Ferrone, Cristina R.; Thayer, Sarah P.; Wargo, Jennifer A.; Sahora, Klaus; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Seefeld, Kimberly J.; Hutter, Mathew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Codman Ctr Clin Effectiveness Surg, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org RI seefeld, kim/J-8127-2014 NR 29 TC 29 Z9 29 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2014 VL 18 IS 1 BP 137 EP 144 DI 10.1007/s11605-013-2336-9 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 285PF UT WOS:000329405400033 PM 24002770 ER PT J AU Lillemoe, KD AF Lillemoe, Keith D. TI "A Debate: Is Surgical Intervention for Cystic Neoplasms of the Pancreas Being Overutilized" SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material DE Pancreatic cystic; Intraductal papillary mucinous neoplasms; Pancreatic cancer ID INTERNATIONAL CONSENSUS GUIDELINES; PAPILLARY MUCINOUS NEOPLASMS; MANAGEMENT C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lillemoe, KD (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM klillemoe@partners.org NR 5 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2014 VL 18 IS 1 BP 181 EP 181 DI 10.1007/s11605-013-2394-z PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 285PF UT WOS:000329405400043 PM 24165873 ER PT J AU Burke, RE Whitfield, E Prochazka, AV AF Burke, Robert E. Whitfield, Emily Prochazka, Allan V. TI Effect of a Hospitalist-Run Postdischarge Clinic on Outcomes SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID PRIMARY-CARE PHYSICIANS; LENGTH-OF-STAY; 30-DAY READMISSION; TRANSITIONAL CARE; PATIENT OUTCOMES; AFTER-DISCHARGE; FOLLOW-UP; CONTINUITY; COMMUNICATION; ASSOCIATION AB BACKGROUNDNew post-discharge strategies to reduce adverse events are needed. OBJECTIVETo determine whether follow-up in a hospitalist-run post-discharge clinic (PDC) decreases post-discharge adverse events when compared to follow-up in a primary care clinic (PCP) or urgent care clinic (UC). DESIGNRetrospective cohort study using propensity scoring in multivariate analysis. PATIENTSConsecutive Veterans discharged home after a nonscheduled admission seen in PDC, UC, or PCP within 30 days of discharge. INTERVENTIONSRecently discharged patients are seen by housestaff who cared for them during the index admission and staffed with a rotating hospitalist in PDC; UC and PCP patients are seen by housestaff or attending ambulatory physicians. MAIN MEASURESThe primary outcome was a composite of hospital readmissions, Emergency Department visits, and mortality 30 days after discharge. KEY RESULTS5085 patients met criteria; 538 followed up in PDC (10.6%), 1848 with their PCP (36.3%), and 2699 in UC (53.1%). Patients following up in PDC were older and had a higher comorbidity burden. ICU exposure was similar between groups. Patients seen in PDC had shorter length of stay (LOS) (PDC, 3.8 days, UC, 5.0 days, PCP, 6.2 days; p = 0.04) and time to first post-discharge visit (PDC, 5.0 days, UC, 9.4 days, PCP, 13.7 days; p < 0.01). There were no differences between groups in the primary outcome in unadjusted or propensity-adjusted multivariate analysis. CONCLUSIONSPatients seen in a hospitalist-run PDC had similar 30-day post-discharge adverse outcome rates despite a 2.4-day shorter LOS compared to patients seen by their PCP. Prospective testing of PDCs is warranted. Journal of Hospital Medicine 2014;9:7-12. (c) 2013 Society of Hospital Medicine C1 [Burke, Robert E.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Hosp Med Sect, Denver, CO USA. [Burke, Robert E.; Prochazka, Allan V.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. [Whitfield, Emily; Prochazka, Allan V.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Div Ambulatory Care, Denver, CO USA. RP Burke, RE (reprint author), Denver VA Med Ctr, Mailstop 111,1055 Clermont St, Denver, CO 80220 USA. EM robert.burke5@va.gov FU Colorado Research Enhancement Award Program FX Dr. Burke had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Dr. Burke was supported by grant funding from the Colorado Research Enhancement Award Program to Improve Care Coordination for Veterans. Initial results of this study were presented at the Society of General Internal Medicine National Meeting in Denver, Colorado, April 24, 2013. NR 28 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2014 VL 9 IS 1 BP 7 EP 12 DI 10.1002/jhm.2099 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 284GD UT WOS:000329303200002 PM 24390821 ER PT J AU Querques, J Kontos, N Freudenreich, O AF Querques, John Kontos, Nicholas Freudenreich, Oliver TI In Reference to "Discharge Against Medical Advice: How Often Do We Intervene?" SO JOURNAL OF HOSPITAL MEDICINE LA English DT Letter C1 [Querques, John] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Querques, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2014 VL 9 IS 1 BP 68 EP 68 DI 10.1002/jhm.2121 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 284GD UT WOS:000329303200013 PM 24339413 ER PT J AU Cuff, P Schmitt, M Zierler, B Cox, M De Maeseneer, J Maine, LL Reeves, S Spencer, HC Thibault, GE AF Cuff, Patricia Schmitt, Madeline Zierler, Brenda Cox, Malcolm De Maeseneer, Jan Maine, Lucinda L. Reeves, Scott Spencer, Harrison C. Thibault, George E. TI Interprofessional education for collaborative practice: views from a global forum workshop SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Editorial Material ID DIAGNOSIS C1 [Cuff, Patricia] Natl Acad Sci, Inst Med, Washington, DC 20418 USA. [Schmitt, Madeline] Univ Rochester, Rochester, NY 14627 USA. [Zierler, Brenda] Univ Washington, Seattle, WA 98195 USA. [Cox, Malcolm] US Dept Vet Affairs, Washington, DC USA. [De Maeseneer, Jan] Univ Ghent, B-9000 Ghent, Belgium. [Maine, Lucinda L.] Amer Assoc Coll Pharm, Washington, DC USA. [Reeves, Scott] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Spencer, Harrison C.] Assoc Sch Publ Hlth, Washington, DC USA. [Thibault, George E.] Josiah Macy Jr Fdn, New York, NY USA. RP Cuff, P (reprint author), Natl Acad Sci, Inst Med, Board Global Hlth, Washington, DC 20418 USA. EM PCuff@nas.edu OI Reeves, Scott/0000-0002-0573-0622 NR 13 TC 1 Z9 1 U1 1 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD JAN PY 2014 VL 28 IS 1 BP 2 EP 4 DI 10.3109/13561820.2013.828910 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 285QE UT WOS:000329407900002 PM 24000878 ER PT J AU Wang, L Devore, S Delgutte, B Colburn, HS AF Wang, Le Devore, Sasha Delgutte, Bertrand Colburn, H. Steven TI Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE inferior colliculus; amplitude modulation; interaural time differences; computational modeling; sound localization ID LATERAL SUPERIOR OLIVE; AMPLITUDE-MODULATED TONES; INTERAURAL TIME SENSITIVITY; COCHLEAR NUCLEUS NEURONS; AUDITORY-NERVE FIBERS; DIFFERENCE SENSITIVITY; BINAURAL INTERACTION; GUINEA-PIG; RESPONSES; COMPLEX AB Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope- ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency. C1 [Wang, Le; Colburn, H. Steven] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Devore, Sasha; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Colburn, HS (reprint author), 44 Cummington St, Boston, MA 02215 USA. EM colburn@bu.edu RI Wang, Le/I-1195-2014; OI , /0000-0003-1349-9608 FU National Institute on Deafness and Other Communication Disorders [5R01 DC-00100, R01 DC-002258, P30 DC-004463, P30 DC-005209]; MIT [T32DC-000038] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants 5R01 DC-00100 (H. S. Colburn), R01 DC-002258 (B. Delgutte), P30 DC-004463 (Boston University), and P30 DC-005209 (Massachusetts Eye and Ear Infirmary). S. Devore was partly supported by training grant T32DC-000038 and by a Helen Carr Peake fellowship from MIT. NR 53 TC 6 Z9 6 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2014 VL 111 IS 1 BP 164 EP 181 DI 10.1152/jn.00450.2013 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 282QS UT WOS:000329188100016 PM 24155013 ER PT J AU Kloosterman, F Layton, SP Chen, Z Wilson, MA AF Kloosterman, Fabian Layton, Stuart P. Chen, Zhe Wilson, Matthew A. TI Bayesian decoding using unsorted spikes in the rat hippocampus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE neural decoding; spatial-temporal Poisson process; population codes; kernel density estimation; spike sorting ID KERNEL DENSITY-ESTIMATION; NEURAL PROSTHETICS; PLACE CELLS; INFORMATION; MOVEMENT; RECORDINGS; EXPERIENCE; FRAMEWORK; ENSEMBLE; MODELS AB A fundamental task in neuroscience is to understand how neural ensembles represent information. Population decoding is a useful tool to extract information from neuronal populations based on the ensemble spiking activity. We propose a novel Bayesian decoding paradigm to decode unsorted spikes in the rat hippocampus. Our approach uses a direct mapping between spike waveform features and covariates of interest and avoids accumulation of spike sorting errors. Our decoding paradigm is nonparametric, encoding model-free for representing stimuli, and extracts information from all available spikes and their waveform features. We apply the proposed Bayesian decoding algorithm to a position reconstruction task for freely behaving rats based on tetrode recordings of rat hippocampal neuronal activity. Our detailed decoding analyses demonstrate that our approach is efficient and better utilizes the available information in the nonsortable hash than the standard sorting-based decoding algorithm. Our approach can be adapted to an online encoding/ decoding framework for applications that require real-time decoding, such as brain-machine interfaces. C1 [Kloosterman, Fabian; Layton, Stuart P.; Chen, Zhe; Wilson, Matthew A.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Kloosterman, Fabian; Layton, Stuart P.; Chen, Zhe; Wilson, Matthew A.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Kloosterman, Fabian] NERF, Louvain, Belgium. [Kloosterman, Fabian] IMEC, Louvain, Belgium. [Kloosterman, Fabian] Katholieke Univ Leuven, Dept Psychol, Lab Biol Psychol, Louvain, Belgium. [Chen, Zhe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA USA. RP Kloosterman, F (reprint author), NERF Imec, Kapeldreef 75, B-3001 Louvain, Belgium. EM fabian.kloosterman@nerf.be OI Chen, Zhe/0000-0002-6483-6056 FU National Institute of Mental Health [MH-061976]; Office of Naval Research MURI [N00014-10-1-0936]; Mathematical Biosciences Institute (MBI); National Science Foundation-CRCNS (Collaborative Research in Computational Neuroscience) grant FX This work was supported by National Institute of Mental Health Grant MH-061976 and Office of Naval Research MURI N00014-10-1-0936 Grant to M. A. Wilson. Z. Chen was supported by an Early Career Award from the Mathematical Biosciences Institute (MBI) and a National Science Foundation-CRCNS (Collaborative Research in Computational Neuroscience) grant. NR 40 TC 15 Z9 15 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2014 VL 111 IS 1 BP 217 EP 227 DI 10.1152/jn.01046.2012 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 282QS UT WOS:000329188100020 PM 24089403 ER PT J AU Popivanov, ID Jastorff, J Vanduffel, W Vogels, R AF Popivanov, Ivo D. Jastorff, Jan Vanduffel, Wim Vogels, Rufin TI Heterogeneous Single-Unit Selectivity in an fMRI-Defined Body-Selective Patch SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INFERIOR TEMPORAL CORTEX; LOCAL-FIELD POTENTIALS; VISUAL-CORTEX; MACAQUE; FACE; OBJECT; REPRESENTATIONS; MONKEYS; REGIONS; CATEGORIZATION AB Although the visual representation of bodies is essential for reproduction, survival, and social communication, little is known about the mechanisms of body recognition at the single neuron level. Imaging studies showed body-category selective regions in the primate occipitotemporal cortex, but it is difficult to infer the stimulus selectivities of the neurons from the population activity measured in these fMRI studies. To overcome this, we recorded single unit activity and local field potentials (LFPs) in the middle superior temporal sulcus body patch, defined by fMRI in the same rhesus monkeys. Both the spiking activity, averaged across single neurons, and LFP gamma power in this body patch was greater for bodies (including monkey bodies, human bodies, mammals, and birds) compared with other objects, which fits the fMRI activation. Single neurons responded to a small proportion of body images. Thus, the category selectivity at the population level resulted from averaging responses of a heterogeneous population of single units. Despite such strong within-category selectivity at the single unit level, two distinct clusters, bodies and nonbodies, were present when analyzing the responses at the population level, and a classifier that was trained using the responses to a subset of images was able to classify novel images of bodies with high accuracy. The body-patch neurons showed strong selectivity for individual body parts at different orientations. Overall, these data suggest that single units in the fMRI-defined body patch are biased to prefer bodies over nonbody objects, including faces, with a strong selectivity for individual body images. C1 [Popivanov, Ivo D.; Jastorff, Jan; Vanduffel, Wim; Vogels, Rufin] Katholieke Univ Leuven, Lab Neuroen Psychofysiol, BE-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vanduffel, Wim] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vogels, R (reprint author), Katholieke Univ Leuven, Lab Neuroen Psychofysiol, BE-3000 Louvain, Belgium. EM Rufin.vogels@med.kuleuven.be OI Jastorff, Jan/0000-0002-3885-9983 FU Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen grant; GOA grant; IUAP grant; PF grant; Agentschap voor Innovatie door Wetenschap en Technologie [101071]; FWO Vlaanderen FX This study was supported by the Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen, GOA, IUAP, and PF grants. I. D. P. was supported by a fellowship from the Agentschap voor Innovatie door Wetenschap en Technologie (Grant 101071) and J.J. is postdoctoral fellow supported by FWO Vlaanderen. We thank M. Docx, I. Puttemans, C. Ulens, B. Correman, D. Kaliukhovich, H. Zivari Adab, P. Kayenbergh, G. Meulemans, W. Depuydt, S. Verstraeten, and M. De Paep for technical support, Dr P. Downing and Dr M. Tarr for providing some of the stimuli, Dr P. A. De Maziere for helping with SVM analysis, and Dr J. Taubert for reading earlier versions of the paper. NR 39 TC 18 Z9 18 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2014 VL 34 IS 1 BP 95 EP 111 DI 10.1523/JNEUROSCI.2748-13.2014 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 282NE UT WOS:000329177800009 PM 24381271 ER PT J AU Quinn, BT Carlson, C Doyle, W Cash, SS Devinsky, O Spence, C Halgren, E Thesen, T AF Quinn, Brian T. Carlson, Chad Doyle, Werner Cash, Sydney S. Devinsky, Orrin Spence, Charles Halgren, Eric Thesen, Thomas TI Intracranial Cortical Responses during Visual-Tactile Integration in Humans SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VENTRAL INTRAPARIETAL AREA; MULTISENSORY INTEGRATION; INTRACEREBRAL POTENTIALS; RARE TARGET; SELECTIVE ATTENTION; SUPERIOR COLLICULUS; MACAQUE MONKEY; HUMAN BRAIN; CORTEX; FMRI AB Sensory integration of touch and sight is crucial to perceiving and navigating the environment. While recent evidence from other sensory modality combinations suggests that low-level sensory areas integrate multisensory information at early processing stages, little is known about how the brain combines visual and tactile information. We investigated the dynamics of multisensory integration between vision and touch using the high spatial and temporal resolution of intracranial electrocorticography in humans. We present a novel, two-step metric for defining multisensory integration. The first step compares the sum of the unisensory responses to the bimodal response as multisensory responses. The second step eliminates the possibility that double addition of sensory responses could be misinterpreted as interactions. Using these criteria, averaged local field potentials and high-gamma-band power demonstrate a functional processing cascade whereby sensory integration occurs late, both anatomically and temporally, in the temporo-parieto-occipital junction (TPOJ) and dorsolateral prefrontal cortex. Results further suggest two neurophysiologically distinct and temporally separated integration mechanisms in TPOJ, while providing direct evidence for local suppression as a dominant mechanism for synthesizing visual and tactile input. These results tend to support earlier concepts of multisensory integration as relatively late and centered in tertiary multimodal association cortices. C1 [Quinn, Brian T.; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Thesen, Thomas] NYU, Dept Neurol, Comprehens Epilepsy Ctr, New York, NY 10016 USA. [Quinn, Brian T.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Halgren, Eric; Thesen, Thomas] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA. [Cash, Sydney S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Spence, Charles] Univ Oxford, Dept Expt Pathol, Oxford, England. [Thesen, Thomas] NYU, Dept Radiol, New York, NY 10016 USA. RP Thesen, T (reprint author), NYU, Dept Neurol, 223 East 34th St, New York, NY 10016 USA. EM thomas.thesen@med.nyu.edu OI Devinsky, Orrin/0000-0003-0044-4632 FU National Institutes of Health [NS18741]; Finding a Cure for Epilepsy & Seizures (FACES) FX This research was supported by grants from National Institutes of Health (Grant NS18741) and Finding a Cure for Epilepsy & Seizures (FACES). We thank Mark Blumberg and Amy Trongnetrpunya for help with data collection. NR 59 TC 9 Z9 9 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2014 VL 34 IS 1 BP 171 EP 181 DI 10.1523/JNEUROSCI.0532-13.2014 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 282NE UT WOS:000329177800017 PM 24381279 ER PT J AU Chung, Y Hancock, KE Nam, SI Delgutte, B AF Chung, Yoojin Hancock, Kenneth E. Nam, Sung-Il Delgutte, Bertrand TI Coding of Electric Pulse Trains Presented through Cochlear Implants in the Auditory Midbrain of Awake Rabbit: Comparison with Anesthetized Preparations SO JOURNAL OF NEUROSCIENCE LA English DT Article DE anesthesia; cochlear implant; inferior colliculus; temporal coding ID INTERAURAL TIME DIFFERENCES; AMPLITUDE-MODULATED TONES; CAT INFERIOR COLLICULUS; TEMPORAL RESOLUTION; RESPONSE PROPERTIES; NEURONAL RESPONSES; CONGENITAL DEAFNESS; PITCH PERCEPTION; STIMULATION; CORTEX AB Cochlear implant (CI) listeners show limits at high frequencies in tasks involving temporal processing such as rate pitch and interaural time difference discrimination. Similar limits have been observed in neural responses to electric stimulation in animals with CI; however, the upper limit of temporal coding of electric pulse train stimuli in the inferior colliculus (IC) of anesthetized animals is lower than the perceptual limit. We hypothesize that the upper limit of temporal neural coding has been underestimated in previous studies due to the confound of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for single-unit studies of IC neurons with electric stimulation through CI. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second. We found that IC neurons in awake rabbits showed higher spontaneous activity and greater sustained responses, both excitatory and suppressive, at high pulse rates. Maximum pulse rates that elicited synchronized responses were approximately two times higher in awake rabbits than in earlier studies with anesthetized animals. Here, we demonstrate directly that anesthesia is a major factor underlying these differences by monitoring the responses of single units in one rabbit before and after injection of an ultra-short-acting barbiturate. In general, the physiological rate limits of IC neurons in the awake rabbit are more consistent with the psychophysical limits in human CI subjects compared with limits from anesthetized animals. C1 [Chung, Yoojin; Hancock, Kenneth E.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Chung, Yoojin; Hancock, Kenneth E.; Nam, Sung-Il; Delgutte, Bertrand] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02115 USA. [Nam, Sung-Il] Keimyung Univ, Sch Med, Dept Otolaryngol, Taegu 700712, South Korea. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Chung, Y (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM yoojin_chung@meei.harvard.edu OI Chung, Yoojin/0000-0002-8772-5308; , /0000-0003-1349-9608 FU National Institutes of Health [R01 DC005775, P30 DC005209]; Massachusetts Eye and Ear (Curing Kids Fund); Hearing Health Foundation FX This work was supported by the National Institutes of Health (Grants R01 DC005775 and P30 DC005209), Massachusetts Eye and Ear (Curing Kids Fund), and the Hearing Health Foundation (Emerging Research Grant to Y. C.). We thank Connie Miller and Melissa McKinnon for technical assistance and Saori Fukuda, Csilla Haburcakova, Andrew McCall, and Michael Kaplan for advice regarding surgical methods for cochlear implantation in rabbits. NR 70 TC 10 Z9 11 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2014 VL 34 IS 1 BP 218 EP 231 DI 10.1523/JNEUROSCI.2084-13.2014 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 282NE UT WOS:000329177800021 PM 24381283 ER PT J AU Yang, JC Ginat, DT Dougherty, DD Makris, N Eskandar, EN AF Yang, Jimmy C. Ginat, Daniel T. Dougherty, Darin D. Makris, Nikos Eskandar, Emad N. TI Lesion analysis for cingulotomy and limbic leucotomy: comparison and correlation with clinical outcomes SO JOURNAL OF NEUROSURGERY LA English DT Article DE cingulotomy; subcaudate tractotomy; limbic leucotomy; psychosurgery; lobotomy; lesion analysis; functional neurosurgery ID OBSESSIVE-COMPULSIVE DISORDER; VOXEL-BASED LESION; STEREOTAXIC SUBCAUDATE TRACTOTOMY; ANTERIOR CINGULATE CORTEX; DEEP BRAIN-STIMULATION; GLUCOSE METABOLIC-RATE; CEREBRAL WHITE-MATTER; TERM-FOLLOW-UP; PREFRONTAL CORTEX; EXTENDED AMYGDALA AB Object. Cingulotomy and limbic leucotomy are lesioning surgeries with demonstrated benefit for medically intractable psychiatric illnesses. They represent significant refinements of the prefrontal lobotomy used from the 1930s through the 1950s. However, the associations between anatomical characterization of these lesions and outcome data are not well understood. To elucidate these procedures and associations, the authors sought to define and compare the neuroanatomy of cingulotomy and limbic leucotomy and to test a method that uses neuroanatomical data and voxel-based lesion-symptom mapping (VLSM) to reveal potential refinements to modern psychiatric neurosurgical procedures. Methods. T1-weighted MR images of patients who had undergone cingulotomy and limbic leucotomy were segmented and registered onto the Montreal Neurological Institute T1-weighted template brain MNI152. Using an atlas-based approach, the authors calculated, by case, the percentage of each anatomical structure affected by the lesion. Because of the infrequency of modern lesion procedures and the requirement for higher-resolution clinical imaging, the sample size was small. The pilot study correlated cingulotomy and limbic leucotomy lesion characteristics with clinical outcomes for patients with obsessive-compulsive disorder. For this study, preoperative and postoperative Yale-Brown Obsessive Compulsive Scale scores for 11 cingulotomy patients and 8 limbic leucotomy patients were obtained, and lesion masks were defined and compared anatomically by using an atlas-based method. Statistically significant voxels were additionally calculated by using VLSM techniques that correlated lesion characteristics with postoperative scores. Results. Mean lesion volumes were 13.3 ml for cingulotomy and 11.8 ml for limbic leucotomy. As expected, cingulotomy was isolated to the anterior cingulum. The subcaudate tractotomy portion of limbic leucotomy additionally affected Brodmann area 25, the medial orbitofrontal cortex, and the nucleus accumbens. Initial results indicated that the dorsolateral regions of the cingulotomy lesion and the posteroventral regions of the subcaudate tractotomy lesion were associated with improved postoperative Yale-Brown Obsessive Compulsive Scale scores. Conclusions. Cingulotomy and limbic leucotomy are lesioning surgeries that target pathological circuits implicated in psychiatric disease. Lesion analysis and VLSM contextualize outcome data and have the potential to be useful for improving lesioning neurosurgical procedures. C1 [Yang, Jimmy C.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Ctr Morphometr Anal, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Imaging, Ctr Morphometr Anal, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Morphometr Anal, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol & Psychiat, Ctr Morphometr Anal, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Yang, Jimmy C.; Dougherty, Darin D.; Makris, Nikos; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA USA. [Makris, Nikos] Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. RP Eskandar, EN (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM eeskandar@partners.org FU National Institute on Drug Abuse [1R01DA027804-01]; National Institute of Mental Health [1R21MH084041-01A1] FX Funding was provided by the National Institute on Drug Abuse (grant no. 1R01DA027804-01 to N.M.) and National Institute of Mental Health (grant no. 1R21MH084041-01A1 to N.M.). NR 91 TC 10 Z9 10 U1 2 U2 7 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2014 VL 120 IS 1 BP 152 EP 163 DI 10.3171/2013.9.JNS13839 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 281GL UT WOS:000329087900023 PM 24236652 ER PT J AU Walcott, BP Neal, JB Sheth, SA Kahle, KT Eskandar, EN Coumans, JV Nahed, BV AF Walcott, Brian P. Neal, Jonathan B. Sheth, Sameer A. Kahle, Kristopher T. Eskandar, Emad N. Coumans, Jean-Valery Nahed, Brian V. TI The incidence of complications in elective cranial neurosurgery associated with dural closure material SO JOURNAL OF NEUROSURGERY LA English DT Article DE dura; pericranium; infection; complication; cerebrospinal fluid; craniotomy; surgical technique ID ACOUSTIC NEUROMA SURGERY; TRAUMATIC BRAIN-INJURY; WOUND-INFECTION; COLLAGEN MATRIX; BLOOD-TRANSFUSION; I MALFORMATION; DURAPLASTY; SUBSTITUTE; SMOKING; TRIAL AB Object. Dural closure with synthetic grafts has been suggested to contribute to the incidence of infection and CSF leak. The objective of this study was to assess the contribution of choice of dural closure material, as well as other factors, to the incidence of infection and CSF leak. Methods. A retrospective, consecutive cohort study of adult patients undergoing elective craniotomy was established between April 2010 and March 2011 at a single center. Exclusion criteria consisted of trauma, bur hole placement alone, and temporary CSF fluid diversion. Results. Three hundred ninety-nine patients were included (mean follow-up 396.6 days). Nonautologous (synthetic) dural substitute was more likely to be used (n = 106) in cases of reoperation (p = 0.001). Seventeen patients developed a surgical site infection and 12 patients developed a CSF leak. Multivariate logistic regression modeling identified estimated blood loss (OR 1.002,95% CI 1.001-1.003; p < 0.001) and cigarette smoking (OR 2.198, 95% CI 1.109-4.238; p = 0.019) as significant predictors of infection. Synthetic dural graft was not a predictor of infection in multivariate analysis. Infratentorial surgery (OR 4.348,95% CI 1.234-16.722; p = 0.024) and more than 8 days of postoperative corticosteroid treatment (OR 3.886, 95% CI 1.052-16.607; p = 0.048) were significant predictors for the development of CSF leak. Synthetic dural graft was associated with a lower likelihood of CSF leak (OR 0.072, 95% CI 0.003-0.552; p = 0.036). Conclusions. The use of synthetic dural closure material is not associated with surgical site infection and is associated with a reduced incidence of CSF leak. Modifiable risk factors exist for craniotomy complications that warrant vigilance and further study. C1 [Walcott, Brian P.; Neal, Jonathan B.; Kahle, Kristopher T.; Eskandar, Emad N.; Coumans, Jean-Valery; Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Neal, Jonathan B.; Kahle, Kristopher T.; Eskandar, Emad N.; Coumans, Jean-Valery; Nahed, Brian V.] Harvard Univ, Sch Med, Boston, MA USA. [Sheth, Sameer A.] Columbia Univ, Med Ctr, Dept Neurosurg, New York, NY USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White Bldg Rm 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 34 TC 5 Z9 5 U1 1 U2 7 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2014 VL 120 IS 1 BP 278 EP 284 DI 10.3171/2013.8.JNS13703 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 281GL UT WOS:000329087900039 PM 24032702 ER PT J AU Guo, JX Guo, N Lang, LX Kiesewetter, DO Xie, QG Li, QZ Eden, HS Niu, G Chen, XY AF Guo, Jinxia Guo, Ning Lang, Lixin Kiesewetter, Dale O. Xie, Qingguo Li, Quanzheng Eden, Henry S. Niu, Gang Chen, Xiaoyuan TI F-18-Alfatide II and F-18-FDG Dual-Tracer Dynamic PET for Parametric, Early Prediction of Tumor Response to Therapy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE dual-tracer dynamic PET; parametric imaging; F-18-alfatide II; F-18-FDG; therapy response ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; INPUT FUNCTIONS; FDG-PET; CHEMOTHERAPY; FEASIBILITY; MICROPET; HYPOXIA; CANCER AB A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with F-18-alfatide II (F-18-AlF-NOTA-E[PEG(4)-c(RGDfk)](2)) and F-18-FDG for parametric monitoring of tumor responses to therapy. Methods: We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with F-18-alfatide II, followed 40 min later by F-18-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of F-18-alfatide II for the 40 min before F-18-FDG injection and then extrapolated to 90 min. The F-18-FDG tumor time-activity curve was isolated from the 90min dual-tracer tumor time-activity curve by subtracting the fitted F-18-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the F-18-alfatide II binding potential (Bp = k(3)/k(4)) and volume of distribution (VD) and F-18-FDG influx rate ((K-1 x k(3))/(k(2) + k(3))) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response. Results: The transport and binding rate parameters K-1-k(3) of F-18-alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and VD correlated well with the parameters from the 60-min single-tracer scan (R-2 > 0.95). Compared with the results of single-tracer PET imaging, F-18-FDG tumor uptake and influx were recovered well from dualtracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of F-18-alfatide II or F-18-FDG were observed, both F-18-alfatide II Bp and F-18-FDG influx from kinetic analysis in tumors showed significant decreases. For therapy of MDA-MB-435 tumors with paclitaxel protein-bound particles, a significant decrease was observed only with F-18-alfatide II Bp value from kinetic analysis but not F-18-FDG influx. Conclusion: The parameters fitted with compartmental modeling from the dual-tracer dynamic imaging are consistent with those from single-tracer imaging, substantiating the feasibility of this methodology. Even though no significant differences in tumor size were found until 5 d after doxorubicin treatment started, at day 3 there were already substantial differences in F-18-alfatide II Bp and F-18-FDG influx rate. Dual-tracer imaging can measure F-18-alfatide II Bp value and F-18-FDG influx simultaneously to evaluate tumor angiogenesis and metabolism. Such changes are known to precede anatomic changes, and thus parametric imaging may offer the promise of early prediction of therapy response. C1 [Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Hubei, Peoples R China. [Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Hubei, Peoples R China. [Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, Natl Inst Hlth NIBIB, Bethesda, MD USA. [Guo, Jinxia; Guo, Ning] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen, Peoples R China. [Li, Quanzheng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Eden, Henry S.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, Natl Inst Hlth NIBIB, Bethesda, MD USA. RP Chen, XY (reprint author), NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU National Key Basic Research Program (973 Project) [2013CB733802]; Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported in part by National Key Basic Research Program (973 Project; 2013CB733802) and by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). No other potential conflict of interest relevant to this article was reported. NR 36 TC 12 Z9 13 U1 1 U2 18 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD JAN 1 PY 2014 VL 55 IS 1 BP 154 EP 160 DI 10.2967/jnumed.113.122069 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 282PG UT WOS:000329183600031 PM 24232871 ER PT J AU Leung, CW Cluggish, S Villamor, E Catalano, PJ Willett, WC Rimm, EB AF Leung, Cindy W. Cluggish, Sarah Villamor, Eduardo Catalano, Paul J. Willett, Walter C. Rimm, Eric B. TI Few Changes in Food Security and Dietary Intake From Short-term Participation in the Supplemental Nutrition Assistance Program Among Low-income Massachusetts Adults SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE Supplemental Nutrition Assistance Program; food security; diet quality; Alternate Healthy Eating Index; food stamps ID GLYCEMIC INDEX; WOMEN; INSECURITY; DISEASE; RISK AB Objective: To examine whether short-term participation in the Supplemental Nutrition Assistance Program (SNAP) affects food security and dietary quality among low-income adults recruited from a Massachusetts-wide emergency food hotline. Methods: A 3-month, longitudinal study was conducted among 107 adults recruited at the time of SNAP application assistance. Outcomes included household food security (10-item US Department of Agriculture Food Security Survey Module), dietary intake (eg, grains, fruit) and diet quality (modified Alternate Healthy Eating Index). Data were analyzed using paired t tests and multivariable linear regression. Results: Supplemental Nutrition Assistance Program participation was not associated with improved household food security over 3 months (P=.25). Compared with non-participants, SNAP participants increased refined grain intake by 1.1 serving/d (P=.02), from baseline to follow-up. No associations were observed with other foods, nutrients, or dietary quality. Conclusion and Implications: Policies that simultaneously improve household food security and dietary quality should be implemented to support the health of low-income Americans participating in this crucial program. C1 [Leung, Cindy W.] Univ Calif San Francisco, Sch Med, Ctr Hlth & Community, San Francisco, CA 94118 USA. [Cluggish, Sarah] Project Bread Walk Hunger, East Boston, MA USA. [Villamor, Eduardo; Willett, Walter C.; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Villamor, Eduardo] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Willett, Walter C.; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter C.; Rimm, Eric B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Willett, Walter C.; Rimm, Eric B.] Harvard Univ, Sch Med, Boston, MA USA. [Leung, Cindy W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Leung, CW (reprint author), Univ Calif San Francisco, Sch Med, Ctr Hlth & Community, 3333 Calif St 465, San Francisco, CA 94118 USA. EM LeungC@chc.ucsf.edu RI Nguyen, Giang/D-9027-2016 FU National Institutes of Health [5 T32 CA009001-35] FX Dr Leung was supported by National Institutes of Health Training Grant 5 T32 CA009001-35. The authors acknowledge Eileen Terchiak and the Project Bread FoodSource Hotline staff for assistance with study recruitment. The authors also sincerely thank the study participants for their participation. NR 20 TC 12 Z9 12 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 EI 1878-2620 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD JAN PY 2014 VL 46 IS 1 BP 68 EP 74 DI 10.1016/j.jneb.2013.10.001 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 282JA UT WOS:000329165900010 PM 24238909 ER PT J AU Pierre, JF Heneghan, AF Feliciano, RP Shanmuganayagam, D Krueger, CG Reed, JD Kudsk, KA AF Pierre, Joseph F. Heneghan, Aaron F. Feliciano, Rodrigo P. Shanmuganayagam, Dhanansayan Krueger, Christian G. Reed, Jess D. Kudsk, Kenneth A. TI Cranberry Proanthocyanidins Improve Intestinal sIgA During Elemental Enteral Nutrition SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE proanthocyanidins; elemental enteral nutrition; secretory IgA; JAK-STAT ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; TOTAL PARENTERAL-NUTRITION; LYMPHOID-TISSUE; DIETARY PROCYANIDINS; ULCERATIVE-COLITIS; MUCOSAL IMMUNITY; GRAPE SEED; JAK-STAT; T-CELLS; POLYPHENOLS AB Background: Elemental enteral nutrition (EEN) decreases gut-associated lymphoid tissue (GALT) function, including fewer Peyer's patch lymphocytes and lower levels of the tissue T helper 2 (Th2) cytokines and mucosal transport protein polymeric immunoglobulin receptor (pIgR), leading to lower luminal secretory immunoglobulin A (sIgA) levels. Since we recently demonstrated that cranberry proanthocyanidins (PACs) maintain the Th2 cytokine interleukin (IL)-4 when added to EEN, we hypothesized the addition of PACs to EEN would normalize other GALT parameters and maintain luminal levels of sIgA. Methods: Institute of Cancer Research mice were randomized (12/group) to receive chow, EEN, or EEN + PACs (100 mg/kg body weight) for 5 days, starting 2 days after intragastric cannulation. Ileum tissue was collected to measure IL-4 by enzyme-linked immunosorbent assay, pIgR by Western blot, and phosphorylated STAT-6 by microarray. Intestinal wash fluid was collected to measure sIgA by Western blot. Results: Compared with chow, EEN significantly decreased tissue IL-4, phosphorylated STAT-6, and pIgR. The addition of PACs to EEN prevented these alterations. Compared with chow, EEN resulted in significantly lower levels of luminal sIgA. The addition of PACs to EEN increased luminal sIgA levels compared with EEN alone. Conclusions: This study suggests the addition of PACs to EEN may support GALT function and maintain intestinal sIgA levels compared with EEN administration alone. C1 [Pierre, Joseph F.; Heneghan, Aaron F.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Pierre, Joseph F.; Feliciano, Rodrigo P.; Shanmuganayagam, Dhanansayan; Krueger, Christian G.; Reed, Jess D.] Univ Wisconsin, Dept Anim Sci, Reed Res Grp, Madison, WI USA. [Feliciano, Rodrigo P.] Univ Wisconsin, Dept Food Sci, Madison, WI 53706 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), H4 736 Clin Sci Ctr, 600 Highland Ave, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu OI Feliciano, Rodrigo/0000-0002-8116-997X FU Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development [I01BX001672]; Reed Research Group FX Supported by award I01BX001672 from the Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development and the Reed Research Group. NR 53 TC 3 Z9 3 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JAN PY 2014 VL 38 IS 1 BP 107 EP 114 DI 10.1177/0148607112473654 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 285AV UT WOS:000329365800012 PM 23359014 ER PT J AU Kadzielski, SM Winter, HS AF Kadzielski, Sarah Mueller Winter, Harland S. TI Novel Methods for Training Future Pediatric Gastroenterologists SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material ID ENDOSCOPY; SKILLS C1 [Kadzielski, Sarah Mueller; Winter, Harland S.] MassGen Hosp Children, Boston, MA 02114 USA. RP Winter, HS (reprint author), MassGen Hosp Children, 175 Cambridge St,CRPZ 5-560, Boston, MA 02114 USA. EM hwinter@partners.org NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JAN PY 2014 VL 58 IS 1 BP 2 EP 3 DI 10.1097/MPG.0000000000000183 PG 2 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 282QR UT WOS:000329188000003 PM 24051486 ER PT J AU Douds, GL Hellkamp, AS Olson, DM Fonarow, GC Smith, EE Schwamm, LH Cockroft, KM AF Douds, G. Logan Hellkamp, Anne S. Olson, DaiWai M. Fonarow, Gregg C. Smith, Eric E. Schwamm, Lee H. Cockroft, Kevin M. TI Venous Thromboembolism in the Get With The Guidelines-Stroke Acute Ischemic Stroke Population: Incidence and Patterns of Prophylaxis SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Deep venous thrombosis; pulmonary embolus; regional variations; treatment variations ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; PLACEBO-CONTROLLED TRIAL; MEDICAL PATIENTS; DOUBLE-BLIND; PREVENTION; DISPARITIES; ENOXAPARIN; DISEASE; REHABILITATION AB Background: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolus (PE), represents a serious complication in hospitalized ischemic stroke patients. This study examines the incidence of VTE and the patterns of VTE prophylaxis in acute ischemic stroke patients deemed appropriate for VTE prophylaxis (nonambulatory) in the Get With The Guidelines-Stroke (GWTG-S) study. Methods: We analyzed data from 149,916 patients who were admitted with acute ischemic stroke and enrolled in GWTG-S from 1259 U. S. hospitals. Patient variables and site characteristics were analyzed in relation to reported administration of VTE prophylaxis. Results: The overall rate of VTE prophylaxis in the analysis cohort was 93% (139,476/149,916). The median site prophylaxis rate was 95%, and prophylaxis rates ranged from 17% (1 site) to 100% (101 sites). Factors associated with increased likelihood of VTE prophylaxis in the multivariable model included history of atrial fibrillation/flutter, receipt of intravenous or intra-arterial tissue plasminogen activator, and admission to an academic hospital. Increasing age, black race, and a history of peripheral vascular disease, diabetes, or stroke were associated with lower likelihood of prophylaxis. Patients receiving care in the Midwest were less likely to receive prophylaxis compared to other regions. Conclusions: Despite a high overall rate of VTE prophylaxis, VTE was found to occur in approximately 3% of GWTG-S patients. Reported rates of VTE prophylaxis differed among hospitals by region and hospital type, and among patients by age, race, and medical comorbidities. C1 [Douds, G. Logan; Cockroft, Kevin M.] Penn State Hershey Med Ctr, Penn State Hershey Stroke Ctr, Hershey, PA 17033 USA. [Hellkamp, Anne S.; Olson, DaiWai M.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary Stroke Program, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Cockroft, KM (reprint author), Penn State Hershey Med Ctr, Dept Neurosurg EC110, POB 859, Hershey, PA 17033 USA. EM kcockroft@psu.edu OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Ortho-McNeil; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Roundtable FX The Get With The Guidelines-Stroke (GWTG-S) program is currently supported in part by a charitable contribution from Ortho-McNeil. GWTG-S has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, and the American Heart Association Pharmaceutical Roundtable. Sponsors did not participate in the design, analysis, manuscript preparation or approval for this project. NR 43 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD JAN PY 2014 VL 23 IS 1 BP 123 EP 129 DI 10.1016/j.jstrokecerebrovasdis.2012.10.018 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 283BQ UT WOS:000329219900027 PM 23253528 ER PT J AU Siller-Matula, JM Trenk, D Krahenbuhl, S Michelson, AD Delle-Karth, G AF Siller-Matula, J. M. Trenk, D. Kraehenbuehl, S. Michelson, A. D. Delle-Karth, G. TI Clinical implications of drug-drug interactions with P2Y(12) receptor inhibitors SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Review DE clopidogrel; drug interactions; P2Y(12) purinoceptor antagonists; platelet aggregation inhibitors; prasugrel; ticagrelor ID CORONARY STENT PLACEMENT; CALCIUM-CHANNEL BLOCKERS; OF-FUNCTION POLYMORPHISM; PROTON PUMP INHIBITORS; PLATELET-FUNCTION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; CLOPIDOGREL PHARMACOKINETICS; ANTIPLATELET ACTION; HEALTHY-VOLUNTEERS AB Polypharmacy in patients undergoing coronary artery stenting or in those presenting with an acute coronary syndrome is common. Nevertheless, the risk of drug-drug interactions in patients treated simultaneously with P2Y(12) receptor inhibitors is less well considered in routine clinical practice. Whereas the irreversible P2Y(12) receptor inhibitors clopidogrel and prasugrel are prodrugs requiring cytochromeP450 (CYP) enzymes for metabolic activation, such activation is not necessary for the direct-acting reversible P2Y(12) receptor inhibitor ticagrelor. Several drugs frequently used in cardiology have been shown to interact with the metabolism of P2Y(12) receptor inhibitors in pharmacodynamic studies. Whereas several drug-drug interactions have been described for clopidogrel and ticagrelor, prasugrel seems to have a low potential for drug-drug interactions. The clinical implications of these interactions have raised concern. In general, concomitant administration of P2Y(12) receptor antagonists and strong inhibitors or inducers of CYP3A/CYP2C19 should be performed with caution in patients treated with clopidogrel/ticagrelor. Under most circumstances, clinicians have the option of prescribing alternative drugs with less risk of drug-drug interactions when used concomitantly with P2Y(12) receptor inhibitors. C1 [Siller-Matula, J. M.; Delle-Karth, G.] Med Univ Vienna, Dept Cardiol, A-1090 Vienna, Austria. [Trenk, D.] Univ Herzzentrum Freiburg Bad Krozingen, Dept Clin Pharmacol, Clin Cardiol, Bad Krozingen, Germany. [Trenk, D.] Univ Herzzentrum Freiburg Bad Krozingen, Dept Clin Pharmacol, Clin Angiol 2, Bad Krozingen, Germany. [Kraehenbuehl, S.] Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland. [Michelson, A. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Div Hematol Oncol,Ctr Plate, Boston, MA 02115 USA. RP Siller-Matula, JM (reprint author), Med Univ Vienna, Dept Cardiol, Wahringergurtel 18-20, A-1090 Vienna, Austria. EM jolanta.siller-matula@meduniwien.ac.at RI Siller-Matula, Jolanta Maria/J-8992-2015 OI Siller-Matula, Jolanta Maria/0000-0001-6041-1635 FU AstraZeneca; Daiichi Sankyo; Eli Lilly; Roche Diagnostics; Bayer Vital; Bristol-Myers Squibb; Boehringer Ingelheim KG; MSD Sharp Dohme; Lilly; GLSynthesis; Takeda FX J. M. Siller-Matula has received lecture or consultant fees from AstraZeneca, Daiichi Sankyo, and Eli Lilly, and a research grant from Roche Diagnostics. D. Trenk has received consulting fees, advisory board fees and lecture fees from Eli Lilly, Daiichi Sankyo, and AstraZeneca, and lecture fees from Bayer Vital, Bristol-Myers Squibb, Boehringer Ingelheim KG, and MSD Sharp & Dohme, in the previous 3 years. His institution receives grant support from Eli Lilly. A. D. Michelson has been principal investigator or co-investigator on research grants to Boston Children's Hospital from GLSynthesis, Lilly, and Takeda, and is a member of the Data Monitoring Board of clinical trials sponsored by Lilly. G. Delle-Karth has received lecture and consultant fees from AstraZeneca and Daiichi Sankyo. S. Krahenbuhl states that he has no conflict of interest. NR 78 TC 19 Z9 19 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2014 VL 12 IS 1 BP 2 EP 13 DI 10.1111/jth.12445 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 285TT UT WOS:000329418600002 PM 24406062 ER PT J AU Kwan, SW Mortell, KE Talenfeld, AD Brunner, MC AF Kwan, Sharon W. Mortell, Kelly E. Talenfeld, Adam D. Brunner, Michael C. TI Thermal Ablation Matches Sub lobar Resection Outcomes in Older Patients with Early-stage Non-small Cell Lung Cancer SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RADIOFREQUENCY ABLATION; MULTICENTER; SURVIVAL; TRIAL; COST AB Purpose: To. compare survival Outcomes of sublobar resection and thermal ablation for early-stage non-small cell lung cancer (NSCLC) in older patients. Materials and Methods: SEER-Medicare linked data for patients with a diagnosis of lung cancer from 2007-2009 were used. Patients >= 65 years old with stage IA or TB NSCLC who were treated with sublobar resection or thermal ablation were identified. Primary outcome was overall survival (OS), and secondary outcome was lung cancer specific survival (LCSS). Demographic and clinical variables were compared. Unadjusted OS and LCSS curves were estimated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox model. OS and LCSS curves for propensity score matched groups were also compared. Results: The final unmatched study population comprised 1,897 patients. Patients Who underwent sublobar resection were significantly younger (P = .006) and significantly less likely to have a comorbidity index > 1 (P = .036), a diagnosis of chronic obstructive pulmonary disease (P = .017), or adjuvant radiation therapy (P < .0001) compared with patients treated with thermal ablation. Unadjusted survival curves of unmatched groups demonstrated significantly better OS (P = .028) and LCSS (P = .0006) in the resection group. Multivariate Cox model adjusting for demographic and clinical variables found no significant difference in OS between the treatment groups (P = .555); a difference in LCSS (hazard ratio = 1.185, P = .026) persisted. Survival curves for matched groups found no significant difference in OS (P = .695) or LCSS (P = .819) between treatment groups. Conclusions: After controlling for selection bias, this study found no difference in OS between patients treated with sublobar resection and thermal ablation. C1 [Kwan, Sharon W.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Mortell, Kelly E.] Univ Hosp Cleveland, Dept Radiol, Case Med Ctr, Cleveland, OH 44106 USA. [Talenfeld, Adam D.] Weill Cornell Med Ctr, Dept Radiol, New York, NY USA. [Brunner, Michael C.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Dept Radiol, Madison, WI 53792 USA. [Brunner, Michael C.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Kwan, SW (reprint author), Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,357115, Seattle, WA 98195 USA. EM shakwan@uw.edu FU Society of Interventional Radiology grant award; National Institutes of Health FX This project was supported by a Society of Interventional Radiology grant award. S.W.K. receives research funding from the National Institutes of Health. None of the authors have identified a conflict of interest. NR 27 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2014 VL 25 IS 1 BP 1 EP 9 DI 10.1016/j.jvir.2013.10.018 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 285FU UT WOS:000329379900001 PM 24365502 ER PT J AU Sheth, RA Walker, TG Saad, WE Dariushnia, SR Ganguli, S Hogan, MJ Hohenwalter, EJ Kalva, SP Rajan, DK Stokes, LS Zuckerman, DA Nikolic, B AF Sheth, Rahul A. Walker, T. Gregory Saad, Wael E. Dariushnia, Sean R. Ganguli, Suvranu Hogan, Mark J. Hohenwalter, Eric J. Kalva, Sanjeeva P. Rajan, Dheeraj K. Stokes, LeAnn S. Zuckerman, Darryl A. Nikolic, Boris CA Soc Interventional Radiology Stand TI Quality Improvement Guidelines for Vascular Access and Closure Device Use SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID SUTURE-MEDIATED CLOSURE; RANDOMIZED CONTROLLED-TRIAL; PERCUTANEOUS CORONARY INTERVENTIONS; CONVENTIONAL MANUAL COMPRESSION; FEMORAL-ARTERY COMPLICATIONS; ARTERIOTOMY CLOSURE; CARDIAC-CATHETERIZATION; PUNCTURE SITE; ANGIO-SEAL; INFECTIOUS COMPLICATIONS C1 [Sheth, Rahul A.; Walker, T. Gregory; Ganguli, Suvranu] Massachusetts Gen Hosp, Dept Radiol, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Saad, Wael E.] Univ Michigan, Med Ctr, Dept Radiol, Ann Arbor, MI 48109 USA. [Dariushnia, Sean R.] Emory Univ, Dept Intervent Radiol & Image Guided Med, Atlanta, GA 30322 USA. [Hogan, Mark J.] Ohio State Univ, Nationwide Childrens Hosp, Dept Radiol, Columbus, OH USA. [Hohenwalter, Eric J.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Dept Radiol, Milwaukee, WI 53226 USA. [Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Rajan, Dheeraj K.] Univ Toronto, Univ Hlth Network, Dept Med Imaging, Toronto, ON, Canada. [Stokes, LeAnn S.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. [Zuckerman, Darryl A.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. RP Walker, TG (reprint author), SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM tgwalker@partners.org NR 81 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2014 VL 25 IS 1 BP 73 EP 84 DI 10.1016/j.jvir.2013.08.011 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 285FU UT WOS:000329379900012 PM 24209907 ER PT J AU McGee, K Haim, H Korioth-Schmitz, B Espy, N Javanbakht, H Letvin, N Sodroski, J AF McGee, Kathleen Haim, Hillel Korioth-Schmitz, Birgit Espy, Nicole Javanbakht, Hassan Letvin, Norman Sodroski, Joseph TI The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; MUCOSAL SHIV CHALLENGE; NEUTRALIZING ANTIBODIES; TYPE-1 ENVELOPE; IN-VIVO; HIV-1 GP120; HETEROSEXUAL TRANSMISSION; LYMPHOCYTE DEPLETION; CORECEPTOR USAGE AB Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favor in vivo persistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by antibodies equivalently and thus were similar in ERantibody. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ERcold nor ERsCD4 significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ERcold and ERsCD4 were counterselected. Remarkably, the virus variant with low ERcold and low ERsCD4 did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ERcold and low ERsCD4. One set of gp120 changes determined the decrease in ERcold and ERsCD4, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ERcold and ERsCD4 may be offset by minimizing the elicitation of autologous neutralizing antibodies. C1 [McGee, Kathleen; Haim, Hillel; Espy, Nicole; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [McGee, Kathleen; Haim, Hillel; Espy, Nicole; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Aids, Boston, MA USA. [Korioth-Schmitz, Birgit; Letvin, Norman] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Sodroski, Joseph] MIT, Ragon Inst MGH, Boston, MA USA. [Sodroski, Joseph] Harvard Univ, Boston, MA USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Javanbakht, Hassan] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 FU National Institutes of Health [AI 24755, AI 67854]; International AIDS Vaccine Initiative; NRSA postdoctoral training program in AIDS research [NIH T32 AI007386] FX This work was supported by the National Institutes of Health (AI 24755 and the Center for HIV/AIDS Vaccine Immunology [AI 67854]), by the International AIDS Vaccine Initiative, and by the late William F. McCarty-Cooper. K. M. and H. H. were supported by an NRSA postdoctoral training program in AIDS research (NIH T32 AI007386). NR 102 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2014 VL 88 IS 1 BP 21 EP 40 DI 10.1128/JVI.01558-13 PG 20 WC Virology SC Virology GA 282SW UT WOS:000329194600003 PM 24131720 ER PT J AU Nakashima, H Chiocca, EA AF Nakashima, Hiroshi Chiocca, E. Antonio TI Switching a Replication-Defective Adenoviral Vector into a Replication-Competent, Oncolytic Adenovirus SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO; MALIGNANT GLIOMA; MAMMALIAN-CELLS; GENE-THERAPY; RECOMBINASE; E1A; EXPRESSION; CANCER; DNA; RESPONSIVENESS AB The adenovirus immediate early gene E1A initiates the program of viral gene transcription and reprograms multiple aspects of cell function and behavior. For adenoviral (Ad) vector-mediated gene transfer and therapy approaches, where replication-defective (RD) gene transfer is required, E1A has thus been the primary target for deletions. For oncolytic gene therapy for cancer, where replication-competent (RC) Ad viral gene expression is needed, E1A has been either mutated or placed under tumor-specific transcriptional control. A novel Ad vector that initially infected target tumor cells in an RD manner for transgene expression but that could be "switched" into an RC, oncolytic state when needed might represent an advance in vector technology. Here, we report that we designed such an Ad vector (proAd Delta 24.GFP), where initial Ad replication is silenced by a green fluorescent protein (GFP) transgene that blocks cytomegalovirus (CMV)-mediated transcription of E1A. This vector functions as a bona fide E1A-deleted RD vector in infected tumor cells. However, because the silencing GFP transgene is flanked by FLP recombination target (FRT) sites, we show that it can be efficiently excised by Flp recombinase site-specific recombination, either when Flp is expressed constitutively in cells or when it is provided in trans by coinfection with a second RD herpes simplex virus (HSV) amplicon vector. This switches the RD Ad, proAd Delta 24. GFP, into a fully RC, oncolytic Ad (rAd Delta 24) that lyses tumor cells in culture and generates oncolytic progeny virions. In vivo, coinfection of established flank tumors with the RD proAd Delta 24.GFP and the RD Flp-bearing HSV1 amplicon leads to generation of RC, oncolytic rAd Delta 24. In an orthotopic human glioma xenograft tumor model, coinjection of the RD proAd Delta 24. GFP and the RD Flp-bearing HSV1 amplicon also led to a significant increase in animal survival, compared to controls. Therefore, Flp-FRT site-specific recombination can be applied to switch RD Ad into fully oncolytic RC Ad for tumor therapy and is potentially applicable to a variety of gene therapy approaches. C1 [Chiocca, E. Antonio] Harvard Inst Med, Dept Neurosurg, Harvey Cushing Neurooncol Labs, Boston, MA USA. Dana Farber Canc Inst, Brigham & Womens Faulkner Hosp, Inst Neurosci Brigham, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Inst Med, Dept Neurosurg, Harvey Cushing Neurooncol Labs, Boston, MA USA. EM EAChiocca@partners.org FU National Institutes of Health [R21NS0632901, 1P01CA163205, P01CA069246] FX This project was supported by National Institutes of Health grants R21NS0632901, 1P01CA163205, and P01CA069246. NR 39 TC 4 Z9 5 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2014 VL 88 IS 1 BP 345 EP 353 DI 10.1128/JVI.02668-13 PG 9 WC Virology SC Virology GA 282SW UT WOS:000329194600031 PM 24155386 ER PT J AU Canny, SP Goel, G Reese, TA Zhang, X Xavier, R Virgin, HW AF Canny, Susan P. Goel, Gautam Reese, Tiffany A. Zhang, Xin Xavier, Ramnik Virgin, Herbert W. TI Latent Gammaherpesvirus 68 Infection Induces Distinct Transcriptional Changes in Different Organs SO JOURNAL OF VIROLOGY LA English DT Article ID HERPESVIRUS-INFECTION; BACTERIAL-INFECTION; GAMMA-HERPESVIRUS; VIRAL-INFECTION; ESTABLISHMENT; PROTECTION; CELLS; PATHOGENESIS; REACTIVATION; MAINTENANCE AB Previous studies identified a role for latent herpesvirus infection in cross-protection against infection and exacerbation of chronic inflammatory diseases. Here, we identified more than 500 genes differentially expressed in spleens, livers, or brains of mice latently infected with gammaherpesvirus 68 and found that distinct sets of genes linked to different pathways were altered in the spleen compared to those in the liver. Several of the most differentially expressed latency-specific genes (e.g., the gamma interferon [IFN-gamma], Cxcl9, and Ccl5 genes) are associated with known latency-specific phenotypes. Chronic herpesvirus infection, therefore, significantly alters the transcriptional status of host organs. We speculate that such changes may influence host physiology, the status of the immune system, and disease susceptibility. C1 [Canny, Susan P.; Reese, Tiffany A.; Zhang, Xin; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Goel, Gautam; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Goel, Gautam; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Goel, Gautam; Xavier, Ramnik] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. RP Virgin, HW (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. EM virgin@wustl.edu FU NIH [CA096511, AI084887, DK043351, F30 HL099019]; Damon Runyon Cancer Research Foundation; NCI Cancer Center Support [P30 CA91842]; ICTS/CTSA from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 TR000448]; NIH Roadmap for Medical Research FX This work was supported by NIH grants CA096511 and AI084887 (to H.V.W.) and DK043351 (to R.X.). S.P.C. is supported by NIH F30 HL099019, and T.A.R. was supported by the Damon Runyon Cancer Research Foundation. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for performing microarrays. The Center is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant UL1 TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. NR 27 TC 4 Z9 5 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2014 VL 88 IS 1 BP 730 EP 738 DI 10.1128/JVI.02708-13 PG 9 WC Virology SC Virology GA 282SW UT WOS:000329194600068 PM 24155394 ER PT J AU Abdel-Mohsen, M Deng, XT Liegler, T Guatelli, JC Salama, MS Ghanem, HEA Rauch, A Ledergerber, B Deeks, SG Guenthard, HF Wong, JK Pillai, SK AF Abdel-Mohsen, Mohamed Deng, Xutao Liegler, Teri Guatelli, John C. Salama, Mohamed S. Ghanem, Hussam El-din A. Rauch, Andri Ledergerber, Bruno Deeks, Steven G. Guenthard, Huldrych F. Wong, Joseph K. Pillai, Satish K. TI Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo SO JOURNAL OF VIROLOGY LA English DT Article ID PERSISTENT LCMV INFECTION; ANTIRETROVIRAL ACTIVITY; PEGINTERFERON ALPHA-2A; RESTRICTION FACTORS; EXPRESSION PROFILE; GENE-EXPRESSION; C VIRUS; SUPPRESSION; BLOCKADE AB Alpha interferon (IFN-alpha) suppresses human immunodeficiency virus type 1 (HIV-1) replication in vitro by inducing cell-intrinsic retroviral restriction mechanisms. We investigated the effects of IFN-alpha/ribavirin (IFN-alpha/riba) treatment on 34 anti-HIV-1 restriction factors in vivo. Expression of several anti-HIV-1 restriction factors was significantly induced by IFN-alpha/riba in HIV/ hepatitis C virus (HCV)-coinfected individuals. Fold induction of cumulative restriction factor expression in CD4+ T cells was significantly correlated with viral load reduction during IFN-alpha/riba treatment (r(2) = 0.649; P < 0.016). Exogenous IFN-alpha induces supraphysiologic restriction factor expression associated with a pronounced decrease in HIV-1 viremia. C1 [Abdel-Mohsen, Mohamed; Liegler, Teri; Deeks, Steven G.; Wong, Joseph K.; Pillai, Satish K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Deng, Xutao; Pillai, Satish K.] Blood Syst Res Inst, San Francisco, CA USA. [Guatelli, John C.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Guatelli, John C.] VA San Diego Healthcare Syst, San Diego, CA USA. [Salama, Mohamed S.; Ghanem, Hussam El-din A.] Ain Shams Univ, Fac Sci, Cairo, Egypt. [Rauch, Andri] Univ Hosp Bern, Dept Infect Dis, CH-3010 Bern, Switzerland. [Rauch, Andri] Univ Bern, Bern, Switzerland. [Ledergerber, Bruno; Guenthard, Huldrych F.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland. [Wong, Joseph K.; Pillai, Satish K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Pillai, SK (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM satish.pillai@ucsf.edu RI Infektiologie, USZ/A-6921-2011; SHCS, int. coll. A/G-4083-2011; SHCS, all/G-4072-2011; Salama, Mohamed/P-7169-2016; Ledergerber, Bruno/B-5656-2009; gunthard, huldrych/F-1724-2011 OI Ledergerber, Bruno/0000-0002-6881-4401; gunthard, huldrych/0000-0002-1142-6723 FU National Institutes of Health [1K01DA024654, R01 AI081668]; University of California, San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research [P30 AI027763]; DARE: Delaney AIDS Research Enterprise (DARE) [U19AI096109]; CFAR Network of Integrated Systems [R24 AI067039]; Swiss HIV Cohort Study Project 594; Swiss National Science Foundation [324730-130865, 33CS30-134277]; Swiss HIV Cohort Study Research Foundation FX This study was supported by grants from the National Institutes of Health (1K01DA024654 and R01 AI081668), the University of California, San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research (P30 AI027763), the DARE: Delaney AIDS Research Enterprise (DARE; U19AI096109), and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by Swiss HIV Cohort Study Project 594 and Swiss National Science Foundation grant 324730-130865. The Swiss HIV Cohort Study is supported by Swiss National Science Foundation grant 33CS30-134277 and the Swiss HIV Cohort Study Research Foundation. NR 22 TC 10 Z9 10 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2014 VL 88 IS 1 BP 763 EP 767 DI 10.1128/JVI.02687-13 PG 5 WC Virology SC Virology GA 282SW UT WOS:000329194600073 PM 24155399 ER PT J AU Clarke, P Leser, JS Quick, ED Dionne, KR Beckham, JD Tyler, KL AF Clarke, Penny Leser, J. Smith Quick, Eamon D. Dionne, Kalen R. Beckham, J. David Tyler, Kenneth L. TI Death Receptor-Mediated Apoptotic Signaling Is Activated in the Brain following Infection with West Nile Virus in the Absence of a Peripheral Immune Response SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) T-CELLS; ACUTE FLACCID PARALYSIS; CENTRAL-NERVOUS-SYSTEM; TOLL-LIKE RECEPTOR-3; GENE-EXPRESSION; ANTIVIRAL RESPONSE; RIG-I; INTERFERON; ENCEPHALITIS; NEURONS AB Apoptosis is an important mechanism of West Nile virus (WNV) pathogenesis within the central nervous system (CNS). The signaling pathways that result in WNV-induced apoptotic neuronal death within the CNS have not been established. In this study, we identified death receptor (DR)-induced apoptosis as a pathway that may be important in WNV pathogenesis, based on the pattern of differential gene expression in WNV-infected, compared to uninfected, brains. Reverse transcription-PCR (RTPCR) and Western blotting confirmed that genes involved in DR-induced apoptotic signaling are upregulated in the brain following WNV infection. Activity of the DR-associated initiator caspase, caspase 8, was also increased in the brains of WNV-infected mice and occurred in association with cleavage of Bid and activation of caspase 9. These results demonstrate that DR-induced apoptotic signaling is activated in the brain following WNV infection and suggest that the caspase 8-dependent cleavage of Bid promotes intrinsic apoptotic signaling within the brains of infected animals. Utilization of a novel ex vivo brain slice culture (BSC) model of WNV encephalitis revealed that inhibition of caspase 8 decreases virus-induced activation of caspase 3 and tissue injury. The BSC model allows us to examine WNV-induced pathogenesis in the absence of a peripheral immune response. Thus, our results indicate that WNV-induced neuronal injury in the brain is mediated by DR-induced apoptosis signaling and can occur in the absence of infiltrating immune cells. However, astrocytes and microglia were activated in WNV-infected BSC, suggesting that local immune responses influence WNV pathogenesis. C1 [Clarke, Penny; Leser, J. Smith; Beckham, J. David; Tyler, Kenneth L.] Univ Colorado Denver, Dept Neurol, Aurora, CO 80045 USA. [Beckham, J. David; Tyler, Kenneth L.] Univ Colorado Denver, Dept Infect Dis, Aurora, CO USA. [Tyler, Kenneth L.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Tyler, Kenneth L.] Univ Colorado Denver, Dept Microbiol, Aurora, CO USA. [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado Denver, Med Scientist Training Program, Aurora, CO USA. [Quick, Eamon D.; Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado Denver, Neurosci Program, Aurora, CO USA. [Tyler, Kenneth L.] Denver VA Med Ctr, Denver, CO USA. RP Clarke, P (reprint author), Univ Colorado Denver, Dept Neurol, Aurora, CO 80045 USA. EM Penny.Clarke@ucdenver.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIH [R01 NS076512, R21 AL101064, F30 NS071630, T32 GM008497, U54 AI065357/RMDP009]; VA merit grant; Reuler-Lewin Family Professorship FX This publication was supported by NIH grants R01 NS076512 (K.L.T.), R21 AL101064 (K.L.T.), F30 NS071630 (K.R.D.), T32 GM008497 (K.R.D.), and U54 AI065357/RMDP009 (D.B.) and by a VA merit grant (K.L.T.). K.L.T. is supported by the Reuler-Lewin Family Professorship. NR 50 TC 14 Z9 14 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2014 VL 88 IS 2 BP 1080 EP 1089 DI 10.1128/JVI.02944-13 PG 10 WC Virology SC Virology GA 282SY UT WOS:000329194900030 PM 24198425 ER PT J AU Brown, JR AF Brown, Jennifer R. TI A new era of treatment for chronic lymphocytic leukaemia? SO LANCET ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jbrown2@partners.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2014 VL 15 IS 1 BP 3 EP 5 DI 10.1016/S1470-2045(13)70558-8 PG 4 WC Oncology SC Oncology GA 281XW UT WOS:000329135300019 PM 24332240 ER PT J AU Landau, DA Carter, SL Getz, G Wu, CJ AF Landau, D. A. Carter, S. L. Getz, G. Wu, C. J. TI Clonal evolution in hematological malignancies and therapeutic implications SO LEUKEMIA LA English DT Review DE cancer evolution; clonal heterogeneity; massively parallel sequencing ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ABL TYROSINE KINASE; CELL LUNG-CANCER; BCR-ABL; MULTIPLE-MYELOMA; BREAST CANCERS; STEM-CELLS; PHILADELPHIA-CHROMOSOME AB The ability of cancer to evolve and adapt is a principal challenge to therapy in general and to the paradigm of targeted therapy in particular. This ability is fueled by the co-existence of multiple, genetically heterogeneous subpopulations within the cancer cell population. Increasing evidence has supported the idea that these subpopulations are selected in a Darwinian fashion, by which the genetic landscape of the tumor is continuously reshaped. Massively parallel sequencing has enabled a recent surge in our ability to study this process, adding to previous efforts using cytogenetic methods and targeted sequencing. Altogether, these studies reveal the complex evolutionary trajectories occurring across individual hematological malignancies. They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the evolutionary process. New insights into this process challenge us to understand the impact of treatment on clonal evolution and inspire the development of novel prognostic and therapeutic strategies. C1 [Landau, D. A.; Wu, C. J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Landau, D. A.; Carter, S. L.; Getz, G.] Broad Inst, Cambridge, MA USA. [Landau, D. A.] Yale Canc Ctr, Dept Hematol, New Haven, CT USA. [Landau, D. A.] Univ Paris Diderot, Paris, France. [Getz, G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Getz, G.] Dept Pathol, Boston, MA USA. [Wu, C. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, C. J.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Room 420,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org FU American Society of Hematology; American Cancer Society; Blavatnik Family Foundation; Lymphoma Research Foundation; NHLBI [1RO1HL103532-01, 1RO1HL116452-01]; NCI [1R01CA155010-01A1]; Leukemia Lymphoma Translational Research Program Award; AACR SU2C Innovative Research Grant FX DAL acknowledges support by the American Society of Hematology (Research Award for Fellows-in-Training), and the American Cancer Society. CJW acknowledges support from the Blavatnik Family Foundation, the Lymphoma Research Foundation, NHLBI (1RO1HL103532-01; 1RO1HL116452-01) and NCI (1R01CA155010-01A1) and is a recipient of a Leukemia Lymphoma Translational Research Program Award and an AACR SU2C Innovative Research Grant. We thank all members of the Broad Institute's Biological Samples and Genome Sequencing Platforms, as well as the Cancer Genome Analysis group who made this work possible (NHGRI-U54HG003067). NR 119 TC 48 Z9 51 U1 0 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2014 VL 28 IS 1 BP 34 EP 43 DI 10.1038/leu.2013.248 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 286CD UT WOS:000329441200003 PM 23979521 ER PT J AU Tai, YT Landesman, Y Acharya, C Calle, Y Zhong, MY Cea, M Tannenbaum, D Cagnetta, A Reagan, M Munshi, AA Senapedis, W Saint-Martin, JR Kashyap, T Shacham, S Kauffman, M Gu, Y Ghobrial, I Zhan, F Kung, AL Schey, SA Richardson, P Munshi, NC Anderson, KC AF Tai, Y-T Landesman, Y. Acharya, C. Calle, Y. Zhong, M. Y. Cea, M. Tannenbaum, D. Cagnetta, A. Reagan, M. Munshi, A. A. Senapedis, W. Saint-Martin, J-R Kashyap, T. Shacham, S. Kauffman, M. Gu, Y. Ghobrial, I. Zhan, F. Kung, A. L. Schey, S. A. Richardson, P. Munshi, N. C. Anderson, K. C. TI CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications SO LEUKEMIA LA English DT Article DE multiple myeloma (MM); selective inhibitors of nuclear export (SINEs) against CRM1/XPO1; osteoclasts (OC); nuclear factor-kappa B (NF-kappa B) activation; nuclear export protein; tumor suppressors ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW MICROENVIRONMENT; NUCLEAR-EXPORT-SIGNAL; DRUG-RESISTANCE; DC-STAMP; EXPRESSION; CANCER; PROTEINS; GENOME; P53 AB The key nuclear export protein CRM1/XPO1 may represent a promising novel therapeutic target in human multiple myeloma (MM). Here we showed that chromosome region maintenance 1 (CRM1) is highly expressed in patients with MM, plasma cell leukemia cells and increased in patient cells resistant to bortezomib treatment. CRM1 expression also correlates with increased lytic bone and shorter survival. Importantly, CRM1 knockdown inhibits MM cell viability. Novel, oral, irreversible selective inhibitors of nuclear export (SINEs) targeting CRM1 (KPT-185, KPT-330) induce cytotoxicity against MM cells (ED50 <200 nM), alone and cocultured with bone marrow stromal cells (BMSCs) or osteoclasts (OC). SINEs trigger nuclear accumulation of multiple CRM1 cargo tumor suppressor proteins followed by growth arrest and apoptosis in MM cells. They further block c-myc, Mcl-1, and nuclear factor kappa B (NF-kappa B) activity. SINEs induce proteasome-dependent CRM1 protein degradation; concurrently, they upregulate CRM1, p53-targeted, apoptosis-related, anti-inflammatory and stress-related gene transcripts in MM cells. In SCID mice with diffuse human MM bone lesions, SINEs show strong anti-MM activity, inhibit MM-induced bone lysis and prolong survival. Moreover, SINEs directly impair osteoclastogenesis and bone resorption via blockade of RANKL-induced NF-kappa B and NFATc1, with minimal impact on osteoblasts and BMSCs. These results support clinical development of SINE CRM1 antagonists to improve patient outcome in MM. C1 [Tai, Y-T; Acharya, C.; Zhong, M. Y.; Cea, M.; Tannenbaum, D.; Cagnetta, A.; Reagan, M.; Munshi, A. A.; Ghobrial, I.; Richardson, P.; Munshi, N. C.; Anderson, K. C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Tai, Y-T; Acharya, C.; Zhong, M. Y.; Cea, M.; Tannenbaum, D.; Cagnetta, A.; Reagan, M.; Munshi, A. A.; Ghobrial, I.; Richardson, P.; Munshi, N. C.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Ctr, Boston, MA 02115 USA. [Landesman, Y.; Senapedis, W.; Saint-Martin, J-R; Kashyap, T.; Shacham, S.; Kauffman, M.] Karyopharm Therapeut Inc, Dept Biol, Natick, MA USA. [Calle, Y.] Kings Coll London, Dept Haematol Med, London, England. [Gu, Y.; Ghobrial, I.] Univ Florida, Shands Canc Ctr, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Zhan, F.; Kung, A. L.] Univ Iowa, Dept Internal Med, Div Hematol Oncol & Blood & Marrow Transplantat, Iowa City, IA 52242 USA. [Schey, S. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr,Dept Pediat Oncol, Boston, MA 02115 USA. Kings Coll Hosp Fdn NHS Trust, Dept Haematol, London, England. RP Tai, YT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02215 USA. EM yu-tzu_tai@dfci.harvard.edu RI Reagan, Michaela/E-3549-2017; OI Munshi, Aditya/0000-0002-9111-7495; Kung, Andrew/0000-0002-9091-488X; Reagan, Michaela/0000-0003-2884-6481 FU National Institutes of Health [RO-1 50947, PO1-78378]; DF/HCC SPORE in Multiple Myeloma [P50CA100707]; Lebow Fund FX We are grateful for Hao Wang, Matt Ma, Michelle Chen, Yiguo Hu and Sunyoung Kong for excellent technical support to the project. We thank the input from Haoqiang Ying and Dilara McCauley from Karyopharm Pharmaceutics. We also thank the nursing staff and clinical research coordinators of the LeBow Institute for Myeloma Therapeutics and the Jerome Lipper Multiple Myeloma Center of the Dana-Farber Cancer Institute for support and help in providing primary tumor specimens for this study. This study was supported by National Institutes of Health Grants RO-1 50947, PO1-78378 and DF/HCC SPORE in Multiple Myeloma P50CA100707; and the Lebow Fund to Cure Myeloma (KCA); KCA is an American Cancer Society Clinical Research Professor. NR 46 TC 67 Z9 68 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2014 VL 28 IS 1 BP 155 EP 165 DI 10.1038/leu.2013.115 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 286CD UT WOS:000329441200016 PM 23588715 ER PT J AU Ok, CY Hasserjian, RP Fox, PS Stingo, F Zuo, Z Young, KH Patel, K Medeiros, LJ Garcia-Manero, G Wang, SA AF Ok, C. Y. Hasserjian, R. P. Fox, P. S. Stingo, F. Zuo, Z. Young, K. H. Patel, K. Medeiros, L. J. Garcia-Manero, G. Wang, S. A. TI Application of the International Prognostic Scoring System-Revised in therapy-related myelodysplastic syndromes and oligoblastic acute myeloid leukemia SO LEUKEMIA LA English DT Letter ID RISK; RELEVANT; FEATURES; CELLS C1 [Ok, C. Y.; Zuo, Z.; Young, K. H.; Patel, K.; Medeiros, L. J.; Wang, S. A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Hasserjian, R. P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fox, P. S.; Stingo, F.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Dept Leukaemia, Houston, TX 77030 USA. RP Ok, CY (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. EM swang5@mdanderson.org RI Stingo, Francesco/D-9475-2017 OI Stingo, Francesco/0000-0001-9150-8552 FU NCI NIH HHS [P30 CA016672] NR 15 TC 19 Z9 19 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2014 VL 28 IS 1 BP 185 EP 189 DI 10.1038/leu.2013.191 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 286CD UT WOS:000329441200021 PM 23787392 ER PT J AU Papp, D Unkelbach, J AF Papp, David Unkelbach, Jan TI Direct leaf trajectory optimization for volumetric modulated arc therapy planning with sliding window delivery SO MEDICAL PHYSICS LA English DT Article DE arc therapy; optimization; sliding window; VMAT ID RADIATION-THERAPY; CLINICAL IMPLEMENTATION; IMRT; GENERATION AB Purpose: The authors propose a novel optimization model for volumetric modulated arc therapy (VMAT) planning that directly optimizes deliverable leaf trajectories in the treatment plan optimization problem, and eliminates the need for a separate arc-sequencing step. Methods: In this model, a 360. arc is divided into a given number of arc segments in which the leaves move unidirectionally. This facilitates an algorithm that determines the optimal piecewise linear leaf trajectories for each arc segment, which are deliverable in a given treatment time. Multileaf collimator constraints, including maximum leaf speed and interdigitation, are accounted for explicitly. The algorithm is customized to allow for VMAT delivery using constant gantry speed and dose rate, however, the algorithm generalizes to variable gantry speed if beneficial. Results: The authors demonstrate the method for three different tumor sites: a head-and-neck case, a prostate case, and a paraspinal case. The authors first obtain a reference plan for intensity modulated radiotherapy (IMRT) using fluence map optimization and 20 intensity-modulated fields in equally spaced beam directions, which is beyond the standard of care. Modeling the typical clinical setup for the treatment sites considered, IMRT plans using seven or nine beams are also computed. Subsequently, VMAT plans are optimized by dividing the 360. arc into 20 corresponding arc segments. Assuming typical machine parameters (a dose rate of 600 MU/min, and a maximum leaf speed of 3 cm/s), it is demonstrated that the optimized VMAT plans with 2-3 min delivery time are of noticeably better quality than the 7-9 beam IMRT plans. The VMAT plan quality approaches the quality of the 20-beam IMRT benchmark plan for delivery times between 3 and 4 min. Conclusions: The results indicate that high quality treatments can be delivered in a single arc with 20 arc segments if sufficient time is allowed for modulation in each segment. c 2014 American Association of Physicists in Medicine. C1 [Papp, David] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Papp, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM Papp.David@mgh.harvard.edu NR 18 TC 9 Z9 9 U1 0 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2014 VL 41 IS 1 AR 4835435 DI 10.1118/1.4835435 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 282OT UT WOS:000329182200006 PM 24387493 ER PT J AU Spadea, MF Verburg, JM Baroni, G Seco, J AF Spadea, Maria Francesca Verburg, Joost Mathias Baroni, Guido Seco, Joao TI The impact of low-Z and high-Z metal implants in IMRT: A Monte Carlo study of dose inaccuracies in commercial dose algorithms SO MEDICAL PHYSICS LA English DT Article DE metal artifacts; metal density; Monte Carlo; dosimetry; IMRT ID ARTIFACT REDUCTION; COMPUTED-TOMOGRAPHY; DOSIMETRIC IMPACT; HIP PROSTHESES; NECK IMRT; RADIOTHERAPY; SUPPRESSION; DENSITY; HEAD AB Purpose: The aim of the study was to evaluate the dosimetric impact of low-Z and high-Z metallic implants on IMRT plans. Methods: Computed tomography (CT) scans of three patients were analyzed to study effects due to the presence of Titanium (low-Z), Platinum and Gold (high-Z) inserts. To eliminate artifacts in CT images, a sinogram-based metal artifact reduction algorithm was applied. IMRT dose calculations were performed on both the uncorrected and corrected images using a commercial planning system (convolution/superposition algorithm) and an in-house Monte Carlo platform. Dose differences between uncorrected and corrected datasets were computed and analyzed using gamma index (P gamma < 1) and setting 2 mm and 2% as distance to agreement and dose difference criteria, respectively. Beam specific depth dose profiles across the metal were also examined. Results: Dose discrepancies between corrected and uncorrected datasets were not significant for low-Z material. High-Z materials caused under-dosage of 20%-25% in the region surrounding the metal and over dosage of 10%-15% downstream of the hardware. Gamma index test yielded P. < 1> 99% for all low-Z cases; while for high-Z cases it returned 91% < P. < 1< 99%. Analysis of the depth dose curve of a single beam for low-Z cases revealed that, although the dose attenuation is altered inside the metal, it does not differ downstream of the insert. However, for high-Z metal implants the dose is increased up to 10%-12% around the insert. In addition, Monte Carlo method was more sensitive to the presence of metal inserts than superposition/convolution algorithm. Conclusions: The reduction in terms of dose of metal artifacts in CT images is relevant for high-Z implants. In this case, dose distribution should be calculated using Monte Carlo algorithms, given their superior accuracy in dose modeling in and around the metal. In addition, the knowledge of the composition of metal inserts improves the accuracy of the Monte Carlo dose calculation significantly. c 2014 American Association of Physicists in Medicine. C1 [Spadea, Maria Francesca] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. [Spadea, Maria Francesca; Verburg, Joost Mathias; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Spadea, Maria Francesca; Verburg, Joost Mathias; Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Baroni, Guido] Politecn Milano Univ, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy. [Baroni, Guido] Fdn CNAO, Bioengn Unit, I-27100 Pavia, Italy. RP Spadea, MF (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. EM mfspadea@unicz.it FU Fulbright fellowship; U.S.-Italy Fulbright Commission FX This work was partly supported by a Fulbright fellowship awarded by the U.S.-Italy Fulbright Commission. The authors would like to thank Karen Doppke (MGH, Boston) and Marta Peroni (PSI, Zurich) for assistance during the data analysis and paper preparation. Authors declare that no conflict of interest exists. NR 22 TC 11 Z9 11 U1 1 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2014 VL 41 IS 1 AR 4829505 DI 10.1118/1.4829505 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 282OT UT WOS:000329182200007 PM 24387494 ER PT J AU Das, PP Shao, Z Beyaz, S Apostolou, E Pinello, L De Los Angeles, A O'Brien, K Atsma, JM Fujiwara, Y Nguyen, M Ljuboja, D Guo, GJ Woo, A Yuan, GC Onder, T Daley, G Hochedlinger, K Kim, J Orkin, SH AF Das, Partha Pratim Shao, Zhen Beyaz, Semir Apostolou, Eftychia Pinello, Luca De Los Angeles, Alejandro O'Brien, Kassandra Atsma, Jennifer Marino Fujiwara, Yuko Minh Nguyen Ljuboja, Damir Guo, Guoji Woo, Andrew Yuan, Guo-Cheng Onder, Tamer Daley, George Hochedlinger, Konrad Kim, Jonghwan Orkin, Stuart H. TI Distinct and Combinatorial Functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in Mouse Embryonic Stem Cell Identity SO MOLECULAR CELL LA English DT Article ID HISTONE DEMETHYLASES; SELF-RENEWAL; DEVELOPMENTAL REGULATORS; TRANSCRIPTIONAL NETWORK; REPROGRAMMING FACTORS; RNAI SCREEN; PLURIPOTENCY; CHROMATIN; POLYCOMB; METHYLATION AB Self-renewal and pluripotency of embryonic stem cells (ESCs) are established by multiple regulatory pathways operating at several levels. The roles of histone demethylases (HDMs) in these programs are incompletely defined. We conducted a functional RNAi screen for HDMs and identified five potential HDMs essential for mouse ESC identity. In-depth analyses demonstrate that the closely related HDMs Jmjd2b and Jmjd2c are necessary for self-renewal of ESCs and induced pluripotent stem cell generation. Genome-wide occupancy studies reveal that Jmjd2b unique, Jmjd2c unique, and Jmjd2b-Jmjd2c common target sites belong to functionally separable Core, Polycomb repressive complex (PRC), and Myc regulatory modules, respectively. Jmjd2b and Nanog act through an interconnected regulatory loop, whereas Jmjd2c assists PRC2 in transcriptional repression. Thus, two HDMs of the same subclass exhibit distinct and combinatorial functions in control of the ESC state. Such complexity of HDM function reveals an aspect of multilayered transcriptional control. C1 [Das, Partha Pratim; Shao, Zhen; Beyaz, Semir; De Los Angeles, Alejandro; O'Brien, Kassandra; Atsma, Jennifer Marino; Fujiwara, Yuko; Minh Nguyen; Ljuboja, Damir; Guo, Guoji; Onder, Tamer; Daley, George; Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Das, Partha Pratim; Shao, Zhen; Beyaz, Semir; De Los Angeles, Alejandro; O'Brien, Kassandra; Atsma, Jennifer Marino; Fujiwara, Yuko; Minh Nguyen; Ljuboja, Damir; Guo, Guoji; Onder, Tamer; Daley, George; Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Div Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Daley, George; Hochedlinger, Konrad; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Apostolou, Eftychia; Daley, George; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Apostolou, Eftychia; Daley, George; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Apostolou, Eftychia; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Ctr Regenerat Med, Boston, MA 02114 USA. [Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Onder, Tamer] Koc Univ, Sch Med, TR-34450 Istanbul, Turkey. [Woo, Andrew] Univ Western Australia, Royal Perth Hosp, Western Australian Inst Med Res, Nedlands, WA 6009, Australia. [Woo, Andrew] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu RI Onder, Tamer /H-3330-2013; OI Onder, Tamer /0000-0002-2372-9158; Beyaz, Semir/0000-0003-4730-4012 FU NIH [HLBI U01HL100001] FX We thank Dan Bauer, Jian Xu for critical reading of the manuscript, and David Hendrix for discussions. We also thank Marc Kerenyi for reagents. We thank F. Abderazzaq and R. Rubio at the Center for Computational Biology sequencing facility at the Dana-Farber Cancer Institute for Illumina HiSeq 2000 sequencing. This work was supported by funding from NIH grant HLBI U01HL100001. S.H.O. is an Investigator of the Howard Hughes Medical Institute. NR 33 TC 22 Z9 22 U1 0 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2014 VL 53 IS 1 BP 32 EP 48 DI 10.1016/j.molcel.2013.11.011 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 286VY UT WOS:000329498600005 PM 24361252 ER PT J AU Gelernter, J Kranzler, HR Sherva, R Almasy, L Koesterer, R Smith, AH Anton, R Preuss, UW Ridinger, M Rujescu, D Wodarz, N Zill, P Zhao, H Farrer, LA AF Gelernter, J. Kranzler, H. R. Sherva, R. Almasy, L. Koesterer, R. Smith, A. H. Anton, R. Preuss, U. W. Ridinger, M. Rujescu, D. Wodarz, N. Zill, P. Zhao, H. Farrer, L. A. TI Genome-wide association study of alcohol dependence: significant findings in African-and European-Americans including novel risk loci SO MOLECULAR PSYCHIATRY LA English DT Article DE alcohol dependence; alcohol-metabolizing enzymes; complex traits; genome-wide association; population differences; population-specific alleles ID DRUG-DEPENDENCE; GENE; SCHIZOPHRENIA; CONSUMPTION; POPULATION; EXPRESSION; DISEASES; CLUSTER; VARIANT; GIRDIN AB We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus, showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P = 1.17 x 10(-31); AAs: Arg369Cys, P = 6.33 x 10(-17)) and ADH1C in AAs (Thr151Thr, P = 4.94 x 10(-10)), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P = 2.63 x 10(-11)), PDLIM5 in EAs (P = 2.01 x 10(-8)), and METAP in AAs (P = 3.35 x 10(-8)). We also identified a novel GWS association (1.17 x 10(-10)) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits. C1 [Gelernter, J.; Smith, A. H.] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, West Haven, CT 06516 USA. [Gelernter, J.; Smith, A. H.] VA CT Healthcare Ctr, West Haven, CT USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Genet, West Haven, CT 06516 USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, West Haven, CT 06516 USA. [Kranzler, H. R.] Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Sherva, R.; Koesterer, R.; Farrer, L. A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Almasy, L.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Anton, R.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Preuss, U. W.; Rujescu, D.] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany. [Preuss, U. W.; Rujescu, D.] Univ Halle Wittenberg, Dept Psychotherapy, D-06108 Halle, Germany. [Preuss, U. W.; Rujescu, D.] Univ Halle Wittenberg, Dept Psychosomat, D-06108 Halle, Germany. [Ridinger, M.; Wodarz, N.] Univ Med Ctr, Dept Psychiat Psychosomat & Psychotherapy, Regensburg, Germany. [Zill, P.] Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany. [Zhao, H.] Yale Univ, Sch Publ Hlth, Dept Biostat, West Haven, CT USA. [Zhao, H.] Yale Univ, Sch Med, Dept Genet, West Haven, CT 06516 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Genet & Genom, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA CT 116A2,950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health [N01-HG-65403, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535]; VA Connecticut and Philadelphia VA MIRECCs; NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; GENEVA Coordinating Center [U01 HG004446]; Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]; Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; Family Study of Cocaine Dependence (FSCD) [R01 DA013423]; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH [HHSN268200782096C] FX We appreciate the work in recruitment and assessment provided at Yale University School of Medicine and the APT Foundation by James Poling, PhD; at McLean Hospital by Roger Weiss, M. D., at the Medical University of South Carolina by Kathleen Brady, MD, Ph.D. and at the University of Pennsylvania by David Oslin, MD. Genotyping services for a part of our GWAS study were provided by the Center for Inherited Disease Research (CIDR) and Yale University (Center for Genome Analysis). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number N01-HG-65403). We are grateful to Ann Marie Lacobelle, Catherine Aldi and Christa Robinson for their excellent technical assistance, to the SSADDA interviewers, led by Yari Nunez and Michelle Slivinsky, who devoted substantial time and effort to phenotype the study sample and to John Farrell and Alexan Mardigan for database management assistance. This study was supported by National Institutes of Health grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535 and the VA Connecticut and Philadelphia VA MIRECCs. The publicly available data sets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0 00092.v1.p1 through dbGaP accession number phs000092.v1.p. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). NR 39 TC 84 Z9 85 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2014 VL 19 IS 1 BP 41 EP 49 DI 10.1038/mp.2013.145 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 279MS UT WOS:000328964700011 PM 24166409 ER PT J AU Szlyk, B Braun, CR Ljubicic, S Patton, E Bird, GH Osundiji, MA Matschinsky, FM Walensky, LD Danial, NN AF Szlyk, Benjamin Braun, Craig R. Ljubicic, Sanda Patton, Elaura Bird, Gregory H. Osundiji, Mayowa A. Matschinsky, Franz M. Walensky, Loren D. Danial, Nika N. TI A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; PANCREATIC BETA-CELLS; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; PROTEIN; LIVER; MUTATIONS; THERAPY; AZD1656; BINDING AB Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin release and hepatic metabolism, and its loss of function is implicated in diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in diabetes; however, clinical data indicate that their benefits can be offset by hypoglycemia, owing to marked allosteric enhancement of the enzyme's glucose affinity. We show that a phosphomimetic of the BCL-2 homology 3 (BH3) alpha-helix derived from human BAD, a GK-binding partner, increases the enzyme catalytic rate without dramatically changing glucose affinity, thus providing a new mechanism for pharmacologic activation of GK. Remarkably, BAD BH3 phosphomimetic mediates these effects by engaging a new region near the enzyme's active site. This interaction increases insulin secretion in human islets and restores the function of naturally occurring human GK mutants at the active site. Thus, BAD phosphomimetics may serve as a new class of GKAs. C1 [Szlyk, Benjamin; Ljubicic, Sanda; Patton, Elaura; Osundiji, Mayowa A.; Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ljubicic, Sanda; Danial, Nika N.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Matschinsky, Franz M.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Walensky, Loren D.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM loren_walensky@dfci.harvard.edu; nika_danial@dfci.harvard.edu FU US National Institutes of Health [R01DK078081, R01GM090299]; Burroughs Wellcome Fund Career Award in Biomedical Sciences; Juvenile Diabetes Research Foundation [17-2011-595]; Claudia Adams Barr Award in Innovative Basic Cancer Research; Stand Up to Cancer Innovative Research Grant; National Sciences and Engineering Research Council of Canada postgraduate scholarship; Swiss National Science Foundation postdoctoral fellowship; Juvenile Diabetes Research Foundation postdoctoral fellowship FX We thank K. Robertson and P. Chen for technical assistance; F. Bernal, S. Devarakonda and C. Buettger for advice on protein purification; E. Gavathiotis, A. West and R. McNally for advice on structural studies; and M. Eck, N. Gray, S. Blacklow, G. Yellen and members of the Danial and Walensky laboratories for valuable discussions. This work was supported by US National Institutes of Health grants R01DK078081 (N. N. D.) and R01GM090299 (L. D. W.), a Burroughs Wellcome Fund Career Award in Biomedical Sciences (N. N. D.), Juvenile Diabetes Research Foundation grant 17-2011-595 (N. N. D.), a Claudia Adams Barr Award in Innovative Basic Cancer Research (N. N. D.), a Stand Up to Cancer Innovative Research Grant (L. D. W.), a National Sciences and Engineering Research Council of Canada postgraduate scholarship (C. R. B.), a Swiss National Science Foundation postdoctoral fellowship (S. L.) and a Juvenile Diabetes Research Foundation postdoctoral fellowship (M.A.O.). NR 56 TC 19 Z9 20 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2014 VL 21 IS 1 BP 36 EP + DI 10.1038/nsmb.2717 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 284BJ UT WOS:000329290700012 PM 24317490 ER PT J AU Wen, PY AF Wen, Patrick Y. TI New Editorial Team for Neuro-Oncology SO NEURO-ONCOLOGY LA English DT Editorial Material C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Patrick_Wen@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2014 VL 16 IS 1 BP 1 EP 1 DI 10.1093/neuonc/not237 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 281YC UT WOS:000329135900001 PM 24366972 ER PT J AU Beiko, J Suki, D Hess, KR Fox, BD Cheung, V Cabral, M Shonka, N Gilbert, MR Sawaya, R Prabhu, SS Weinberg, J Lang, FF Aldape, KD Sulman, EP Rao, G McCutcheon, IE Cahill, DP AF Beiko, Jason Suki, Dima Hess, Kenneth R. Fox, Benjamin D. Cheung, Vincent Cabral, Matthew Shonka, Nicole Gilbert, Mark R. Sawaya, Raymond Prabhu, Sujit S. Weinberg, Jeffrey Lang, Frederick F. Aldape, Kenneth D. Sulman, Erik P. Rao, Ganesh McCutcheon, Ian E. Cahill, Daniel P. TI IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection SO NEURO-ONCOLOGY LA English DT Article DE anaplastic astrocytoma; IDH1; glioblastoma; malignant glioma; surgical resection ID INTEGRATED GENOMIC ANALYSIS; CODON 132 MUTATION; GLIOBLASTOMA-MULTIFORME; ANAPLASTIC ASTROCYTOMAS; RADIATION-THERAPY; GLIOMAS; EXTENT; OLIGODENDROGLIOMA; TEMOZOLOMIDE; TUMORS AB IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomasuWorld Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma. Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n 128 anaplastic astrocytomas and n 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry. IDH1 mutation was independently associated with complete resection of enhancing disease (93 complete resections among mutants vs 67 among wild-type, P .001), indicating IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor on survival differed between IDH1 wild-type and mutant tumors. Complete resection of enhancing disease among IDH1 wild-type tumors was associated with a median survival of 19.6 months versus 10.7 months for incomplete resection; however, no survival benefit was observed in association with further resection of nonenhancing disease (minimization of total tumor volume). In contrast, IDH1 mutants displayed an additional survival benefit associated with maximal resection of total tumor volume (median survival 9.75 y for 5 cc residual vs not reached for 5 cc, P .025). The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status. C1 [Beiko, Jason; Suki, Dima; Fox, Benjamin D.; Cheung, Vincent; Cabral, Matthew; Sawaya, Raymond; Prabhu, Sujit S.; Weinberg, Jeffrey; Lang, Frederick F.; Rao, Ganesh; McCutcheon, Ian E.; Cahill, Daniel P.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Aldape, Kenneth D.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Hess, Kenneth R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Sulman, Erik P.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Shonka, Nicole; Gilbert, Mark R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Cabral, Matthew; Sawaya, Raymond; Lang, Frederick F.; Aldape, Kenneth D.; Sulman, Erik P.; Rao, Ganesh; Cahill, Daniel P.] Univ Texas Houston, MD Anderson Canc Ctr, Brain Tumor Res Ctr, Houston, TX 77030 USA. [Fox, Benjamin D.; Cheung, Vincent; Sawaya, Raymond] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. [Shonka, Nicole] Nebraska Canc Ctr, Dept Oncol, Omaha, NE USA. RP Cahill, DP (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr Neurooncol, Dept Neurosurg, 32 Fruit St Yawkey 9E, Boston, MA 02114 USA. EM cahill@mgh.harvard.edu RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Weinberg, Jeffrey/0000-0001-5587-6673; Cahill, Daniel/0000-0003-2552-6546 FU Burroughs Wellcome Trust; James S. McDonnell Foundation; Texas Neurofibromatosis Foundation FX This work was supported by funding from the Burroughs Wellcome Trust, the James S. McDonnell Foundation, and the Texas Neurofibromatosis Foundation. NR 47 TC 60 Z9 60 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2014 VL 16 IS 1 BP 81 EP 91 DI 10.1093/neuonc/not159 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 281YC UT WOS:000329135900011 PM 24305719 ER PT J AU Arafat, SN Suelves, AM Spurr-Michaud, S Chodosh, J Foster, CS Dohlman, CH Gipson, IK AF Arafat, Samer N. Suelves, Ana M. Spurr-Michaud, Sandra Chodosh, James Foster, C. Stephen Dohlman, Claes H. Gipson, Ilene K. TI Neutrophil Collagenase, Gelatinase, and Myeloperoxidase in Tears of Patients with Stevens-Johnson Syndrome and Ocular Cicatricial Pemphigoid SO OPHTHALMOLOGY LA English DT Article ID TOXIC EPIDERMAL NECROLYSIS; MATRIX METALLOPROTEINASES; VERNAL KERATOCONJUNCTIVITIS; CONJUNCTIVAL INFLAMMATION; DRY EYE; FLUID; DISEASE; SURFACE; MATRIX-METALLOPROTEINASE-9; ACTIVATION AB Objective: To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Design: Prospective, noninterventional cohort study. Participants: Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes). Methods: Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immunosorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were performed between the various analytes within study groups. Main Outcome Measures: Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8-to-TIMP-1 ratio; MMP-9-to-TIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO. Results: MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS> OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8-to-TIMP-1 and MMP9-to-TIMP- 1 ratios were markedly elevated in SJS and OCP tears (SJS> OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO. Conclusions: Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation. (C) 2014 by the American Academy of Ophthalmology. C1 [Arafat, Samer N.; Spurr-Michaud, Sandra; Gipson, Ilene K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Arafat, Samer N.; Chodosh, James; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Suelves, Ana M.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Foster, C. Stephen] Ocular Immunol & Uveitis Fdn, Cambridge, MA USA. RP Gipson, IK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM ilene_gipson@meei.harvard.edu FU Boston Keratoprosthesis Research Fund; Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; National Eye Institute, National Institutes of Health, Bethesda, Maryland [NEI 03306] FX Supported by The Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, and the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: NEI 03306 [I.K.G.]). NR 44 TC 15 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2014 VL 121 IS 1 BP 79 EP 87 DI 10.1016/j.ophtha.2013.06.049 PG 9 WC Ophthalmology SC Ophthalmology GA 282KG UT WOS:000329169500020 PM 23962653 ER PT J AU Stryjewski, TP Andreoli, CM Eliott, D AF Stryjewski, Tomasz P. Andreoli, Christopher M. Eliott, Dean TI Retinal Detachment after Open Globe Injury SO OPHTHALMOLOGY LA English DT Article ID OCULAR TRAUMA; CLASSIFICATION; REGRESSION; SURVIVAL AB Purpose: To characterize the development of retinal detachment (RD) after open globe trauma. Design: Case-control study. Participants: A total of 892 patients comprising 893 open globe injuries (OGIs), of whom 255 were ultimately diagnosed with RD, with the remaining eyes serving as controls. Methods: Retrospective chart review of patients with OGIs presenting to the Massachusetts Eye and Ear Infirmary between 1999 and 2011. Kaplane-Meier analysis was used to estimate the time to detachment, and multivariable logistic regression was used to define the clinical factors associated with RD after OGI. Main Outcome Measures: Demographic and clinical characteristics at the time of presentation after OGI, date of RD diagnosis, and last date of follow-up. Results: Primary repair of the open globe was typically undertaken within hours of presentation. A total of 255 eyes were ultimately diagnosed with RD after open globe trauma, yielding an incidence of 29% (95% confidence interval, 26-32). For eyes that developed RD, 27% (69/ 255) detached within 24 hours of primary open globe repair, 47% (119/ 255) detached within 1 week, and 72% (183/ 255) detached within 1 month. Multivariable regression analysis revealed the presence of vitreous hemorrhage (odds ratio [OR], 7.29; P< 0.001), higher zone of injury (OR, 2.51 per integer increase in zone number; OR, 1.00-6.30; P< 0.001), and poorer logarithm of the minimum angle of resolution (logMAR) visual acuity at the time of presentation after OGI (OR, 2.41 per integer increase in logMAR visual acuity; OR, 1.00-81.30; P< 0.001) to be associated with RD. A screening tool was created: the Retinal Detachment after Open Globe Injury score. Conclusions: Retinal detachment is common after open globe trauma, although often not appearing until days to weeks after the initial traumatic event. Several clinical variables at the time of initial presentation can predict the future risk of detachment. (C) 2014 by the American Academy of Ophthalmology. C1 [Stryjewski, Tomasz P.; Andreoli, Christopher M.; Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Stryjewski, Tomasz P.; Andreoli, Christopher M.; Eliott, Dean] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Andreoli, Christopher M.] Harvard Vanguard Med Associates, Boston, MA USA. RP Eliott, D (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences); Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Institutes of Health Award) [8UL1TR000170-05]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (Harvard University) FX This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. NR 25 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2014 VL 121 IS 1 BP 327 EP 333 DI 10.1016/j.ophtha.2013.06.045 PG 7 WC Ophthalmology SC Ophthalmology GA 282KG UT WOS:000329169500052 PM 24011994 ER PT J AU Mori, T Ishii, S Greendale, GA Cauley, JA Sternfeld, B Crandall, CJ Han, W Karlamangla, AS AF Mori, T. Ishii, S. Greendale, G. A. Cauley, J. A. Sternfeld, B. Crandall, C. J. Han, W. Karlamangla, A. S. TI Physical activity as determinant of femoral neck strength relative to load in adult women: findings from the hip strength across the menopause transition study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Active living; Composite strength indices; Femoral neck strength relative to load; Peak bone strength; Physical activity ID BONE-MINERAL DENSITY; FRACTURE RISK-ASSESSMENT; FINAL MENSTRUAL PERIOD; BODY-MASS INDEX; OSTEOPOROTIC FRACTURES; MULTIETHNIC COHORT; RANCHO-BERNARDO; CALCIUM INTAKE; HEALTH; PREMENOPAUSAL AB Our objective was to examine associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Greater physical activity in each of the domains of sport, active living, home, and work was associated with higher peak femoral neck strength relative to load. Our objective was to examine the associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Composite indices of femoral neck strength integrate body size with femoral neck size and bone mineral density to gauge bone strength relative to load during a fall, and are inversely associated with incident fracture risk. Participants were 1,919 pre- and early perimenopausal women from the Study of Women's Health Across the Nation. Composite indices of femoral neck strength relative to load in three failure modes (compression, bending, and impact) were created from hip dual-energy X-ray absorption scans and body size. Usual physical activity within the past year was assessed with the Kaiser Physical Activity Survey in four domains: sport, home, active living, and work. We used multiple linear regression to examine the associations. Greater physical activity in each of the four domains was independently associated with higher composite indices, adjusted for age, menopausal transition stage, race/ethnicity, Study of Women's Health Across the Nation study site, smoking status, smoking pack-years, alcohol consumption level, current use of supplementary calcium, current use of supplementary vitamin D, current use of bone-adverse medications, prior use of any sex steroid hormone pills or patch, prior use of depo-provera injections, history of hyperthyroidism, history of previous adult fracture, and employment status: standardized effect sizes ranged from 0.04 (p < 0.05) to 0.20 (p < 0.0001). Physical activity in each domain examined was associated with higher peak femoral neck strength relative to load in pre- and early perimenopausal women. C1 [Mori, T.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Mori, T.; Greendale, G. A.; Han, W.; Karlamangla, A. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Ishii, S.] Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Bunkyo Ku, Tokyo 1138655, Japan. [Cauley, J. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Sternfeld, B.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Crandall, C. J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. RP Mori, T (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, 11301 Wilshire Blvd,Bldg B220 11 G, Los Angeles, CA 90073 USA. EM takahiromori@outlook.com RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; NIA [AG026463]; VA Advanced Fellowship Program in Geriatrics; VA Greater Los Angeles Geriatric Research Education and Clinical Center FX The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH) (grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). The Hip Strength Through the Menopausal Transition has grant support from the NIA (AG026463). Takahiro Mori was supported by the VA Advanced Fellowship Program in Geriatrics and the VA Greater Los Angeles Geriatric Research Education and Clinical Center. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, VA, or the NIH. We thank the study staff at each site and all the women who participated in SWAN. NR 43 TC 7 Z9 7 U1 0 U2 7 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2014 VL 25 IS 1 BP 265 EP 272 DI 10.1007/s00198-013-2429-z PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 281MP UT WOS:000329106000025 PM 23812598 ER PT J AU Hashmi, JA Davis, KD AF Hashmi, Javeria A. Davis, Karen D. TI Deconstructing sex differences in pain sensitivity SO PAIN LA English DT Review ID GENDER-DIFFERENCES; MUSCULOSKELETAL PAIN; RISK-FACTORS; HEAT PAIN; PERCEPTION; WOMEN; MEN; DISCRIMINATION; HYPERALGESIA; SEX/GENDER C1 [Hashmi, Javeria A.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. [Hashmi, Javeria A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Davis, Karen D.] Univ Hlth Network, Toronto Western Hosp, Toronto Western Res Inst, Div Brain Imaging & Behav Syst Neurosci, Toronto, ON M5T 2S8, Canada. [Davis, Karen D.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Davis, Karen D.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. RP Davis, KD (reprint author), Univ Hlth Network, Toronto Western Hosp, Toronto Western Res Inst, Div Brain Imaging & Behav Syst Neurosci, 399 Bathurst St,Room MP14-306, Toronto, ON M5T 2S8, Canada. EM kdavis@uhnres.utoronto.ca FU Canadian Institutes of Health Research FX This work was supported by the Canadian Institutes of Health Research. NR 50 TC 12 Z9 13 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JAN PY 2014 VL 155 IS 1 BP 10 EP 13 DI 10.1016/j.pain.2013.07.039 PG 4 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 282YE UT WOS:000329210000006 PM 23891901 ER PT J AU Ghoshhajra, BB Lee, AM Engel, LC Celeng, C Kalra, MK Brady, TJ Hoffmann, U Westra, SJ Abbara, S AF Ghoshhajra, Brian B. Lee, Ashley M. Engel, Leif-Christopher Celeng, Csilla Kalra, Mannudeep K. Brady, Thomas J. Hoffmann, Udo Westra, Sjirk J. Abbara, Suhny TI Radiation Dose Reduction in Pediatric Cardiac Computed Tomography: Experience from a Tertiary Medical Center SO PEDIATRIC CARDIOLOGY LA English DT Article DE Cardiac computed tomography angiography; Pediatrics; Children; Low dose; Radiation ID CONGENITAL HEART-DISEASE; DUAL-SOURCE CT; CARDIOVASCULAR MAGNETIC-RESONANCE; CORONARY-ANGIOGRAPHY; IMAGE QUALITY; SHOOT MODE; HIGH-PITCH; TEMPORAL RESOLUTION; CHILDREN; PROTECTION AB Cardiac CT angiography (cCTA) has become an established method for the assessment of congenital heart disease. However, the potential harmful effects of ionizing radiation must be considered, particularly in younger, more radiosensitive patients. In this study, we sought to assess the temporal change in radiation doses from pediatric cCTA during an 8-year period at a tertiary medical center. This retrospective study included all patients a parts per thousand currency sign18 years old who were referred to electrocardiography (ECG)-gated cCTA for the assessment of congenital heart disease or inflammatory disease (Kawasaki disease) from November 2004 to September 2012. During the study period, 95 patients were scanned using 3 different scanner models-64-slice multidetector CT (64-MDCT) and first- (64-DSCT) and second-generation (128-DSCT) dual-source CT-and 3 scan protocols-retrospective ECG-gated helical scanning (RG), prospective ECG-triggered axial scanning (PT), or prospective ECG-triggered high-pitch helical scanning (HPH). Effective dose (ED) was calculated with the dose length product method with a conversion factor (k) adjusted for age. ED was then compared among scan protocols. Image quality was extracted from clinical cCTA reports when available. Overall, 94 % of scans were diagnostic (80 % for 64-slice MDCT, 93 % for 64-slice DSCT, and 97 % for 128-slice DSCT).With 128-DSCT, median ED (1.0 [range 0.6-2.0] mSv) decreased by 85.8 % and 66.8 % compared with 64-MDCT (6.8 [range 2.9-13.6] mSv) and 64-DSCT (2.9 [range 0.9-4.1] mSv), respectively. With HPH, median ED (0.9 [range 0.6-1.8] mSv) decreased by 59.4 % and 85.4 % compared with PT (2.2 [range 0.9-3.4] mSv) and RG (6.1 [range 2.5-10.6] mSv). cCTA can now be obtained at very low radiation doses in pediatric patients using the latest dual-source CT technology in combination with prospective ECG-triggered HPH acquisition. C1 [Ghoshhajra, Brian B.; Lee, Ashley M.; Engel, Leif-Christopher; Celeng, Csilla; Kalra, Mannudeep K.; Brady, Thomas J.; Hoffmann, Udo; Westra, Sjirk J.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Lee, AM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM amshlee@hotmail.com NR 49 TC 19 Z9 20 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0172-0643 EI 1432-1971 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD JAN PY 2014 VL 35 IS 1 BP 171 EP 179 DI 10.1007/s00246-013-0758-5 PG 9 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA 285EA UT WOS:000329374800026 PM 23872908 ER PT J AU Hacker, KA Penfold, R Arsenault, L Zhang, F Murphy, M Wissow, L AF Hacker, Karen A. Penfold, Robert Arsenault, Lisa Zhang, Fang Murphy, Michael Wissow, Larry TI Screening for Behavioral Health Issues in Children Enrolled in Massachusetts Medicaid SO PEDIATRICS LA English DT Article DE behavioral health; screening; primary care; medicaid ID PEDIATRIC SYMPTOM CHECKLIST; MENTAL-HEALTH; FOSTER-CARE; ADOLESCENTS; RACE/ETHNICITY; POPULATION; DISORDERS; SERVICES; SYSTEM AB OBJECTIVES: To understand mandated behavioral health (BH) screening in Massachusetts Medicaid including characteristics of screened children, predictors of positive screens, and whether screening identifies children without a previous BH history. METHODS: Massachusetts mandated BH screening in particularly among underidentified groups. 2008. Providers used a billing code and modifier to indicate a completed screen and whether a BH need was identified. Using MassHealth claims data, children with >= 300 days of eligibility in fiscal year (FY) 2009 were identified and categorized into groups based on first use of the modifier, screening code, or claim. Bivariate analyses were conducted to determine differences among groups. BH history was examined by limiting the sample to those continuously enrolled in FY 2008 and 2009. Multivariate logistic regression was used to determine predictors of positive screens. RESULTS: Of 355 490 eligible children, 46% had evidence of screening. Of those with modifiers, 12% were positive. Among continuously enrolled children (FY 2008 and FY 2009) with evidence of screening, 43% with positive modifiers had no BH history. This "newly identified" group were more likely to be female, younger, minority, and from rural residences (P < .0001). Among children with modifiers; gender (male), age (5-7), being in foster care, recent BH history, and Hispanic ethnicity predicted having a positive modifier. CONCLUSIONS: The high rate of newly identified Medicaid children with a BH need suggests that screening is performing well, particularly among underidentified groups. To better assess screening value, future work on cost-effectiveness and the impact on subsequent mental health treatment is needed. C1 [Hacker, Karen A.] Allegheny Cty Hlth Dept, Pittsburgh, PA 15213 USA. [Hacker, Karen A.; Arsenault, Lisa] Inst Community Hlth, Cambridge, MA USA. [Hacker, Karen A.; Arsenault, Lisa; Zhang, Fang; Murphy, Michael] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zhang, Fang] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Penfold, Robert] Grp Hlth Res Inst, Seattle, WA USA. [Penfold, Robert] Univ Washington, Dept Hlth Serv Res, Seattle, WA 98195 USA. [Arsenault, Lisa] Cambridge Hlth Alliance, Cambridge, MA USA. [Zhang, Fang] Harvard Pilgrim Healthcare Inst, Boston, MA USA. [Murphy, Michael] Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. [Wissow, Larry] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Hacker, KA (reprint author), Allegheny Cty Hlth Dept, 3333 Forbes Ave, Pittsburgh, PA 15213 USA. EM Khacker@achd.net FU Bennett Foundation; National Institute of Mental Health [P20 MH086048, R21MH094942]; Institute for Community Health, and Massachusetts Department of Mental Health; National Institutes of Health (NIH) FX Supported by Bennett Foundation, National Institute of Mental Health grants P20 MH086048 and R21MH094942, Institute for Community Health, and Massachusetts Department of Mental Health. Funded by the National Institutes of Health (NIH). NR 37 TC 10 Z9 10 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2014 VL 133 IS 1 BP 46 EP 54 DI 10.1542/peds.2013-1180 PG 9 WC Pediatrics SC Pediatrics GA 282JX UT WOS:000329168400043 PM 24298005 ER PT J AU Grant, CC Stewart, AW Scragg, R Milne, T Rowden, J Ekeroma, A Wall, C Mitchell, EA Crengle, S Trenholme, A Crane, J Camargo, CA AF Grant, Cameron C. Stewart, Alistair W. Scragg, Robert Milne, Tania Rowden, Judy Ekeroma, Alec Wall, Clare Mitchell, Edwin A. Crengle, Sue Trenholme, Adrian Crane, Julian Camargo, Carlos A., Jr. TI Vitamin D During Pregnancy and Infancy and Infant Serum 25-Hydroxyvitamin D Concentration SO PEDIATRICS LA English DT Article DE vitamin D; 25-hydroxyvitamin D; pregnancy; infancy; supplementation ID BREAST-FED INFANTS; BONE-MINERAL CONTENT; D DEFICIENCY; D SUPPLEMENTATION; HYPOVITAMINOSIS D; HIGH PREVALENCE; HUMAN-MILK; WOMEN; CALCIUM; HEALTHY AB OBJECTIVE: To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D (25(OH) D) concentration >= 20 ng/mL during infancy. METHODS: A randomized, double-blind, placebo-controlled trial in New Zealand. Pregnant mothers, from 27 weeks' gestation to birth, and then their infants, from birth to age 6 months, were randomly assigned to 1 of 3 mother/infant groups: placebo/placebo, vitamin D3 1000/400 IU, or vitamin D3 2000/800 IU. Serum 25(OH) D and calcium concentrations were measured at enrollment, 36 weeks' gestation, in cord blood, and in infants at 2, 4, and 6 months of age. RESULTS: Two-hundred-and-sixty pregnant women were randomized. At enrollment, the proportions with serum 25(OH) D >= 20 ng/mL for placebo, lower-dose, and higher-dose groups were 54%, 64%, and 55%, respectively. The proportion with 25(OH) D >= 20 ng/mL was larger in both intervention groups at 36 weeks' gestation (50%, 91%, 89%,P < 001). In comparison with placebo, the proportion of infants with 25(OH) D >= 20 ng/mL was larger in both intervention groups to age 4 months: cord blood (22%, 72%, 71%, P < 001), 2 months (50%, 82%, 92%, P < 001), and 4 months (66%, 87%, 87%, P = .004), but only in the higher-dose group at age 6 months (74%, 82%, 89%, P =. 07; higher dose versus placebo P =.03, lower dose versus placebo P = .21). CONCLUSIONS: Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH) D >= 20 ng/mL, with the higher dose sustaining this increase for longer. C1 [Grant, Cameron C.; Stewart, Alistair W.; Scragg, Robert; Milne, Tania; Rowden, Judy; Ekeroma, Alec; Wall, Clare; Mitchell, Edwin A.] Univ Auckland, Auckland 1142, New Zealand. [Crengle, Sue] Univ Auckland, Te Kupenga Hauora Maori, Auckland 1142, New Zealand. [Trenholme, Adrian] Middlemore Hosp, Auckland 6, New Zealand. [Crane, Julian] Univ Otago, Wellington, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Grant, CC (reprint author), Univ Auckland, Fac Med & Hlth Sci, Dept Paediat Child & Youth Hlth, Private Bag 92019,Wellesley St, Auckland 1142, New Zealand. EM cc.grant@auckland.ac.nz OI Ekeroma, Alec/0000-0002-7581-8275; Scragg, Robert/0000-0003-0013-2620; Grant, Cameron/0000-0002-4032-7230 FU Health Research Council of New Zealand [09/215R]; Cure Kids FX The pregnancy and infancy vitamin study was funded by the Health Research Council of New Zealand, grant number 09/215R. Dr Mitchell is supported by Cure Kids. The funder played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Study medicine was prepared by the Ddrops Company (Woodbridge, Ontario, Canada). NR 49 TC 31 Z9 32 U1 1 U2 15 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2014 VL 133 IS 1 BP E143 EP E153 DI 10.1542/peds.2013-2602 PG 11 WC Pediatrics SC Pediatrics GA 282JX UT WOS:000329168400019 PM 24344104 ER PT J AU Venkatesh, KK Zlotnick, C Triche, EW Ware, C Phipps, MG AF Venkatesh, Kartik K. Zlotnick, Caron Triche, Elizabeth W. Ware, Crystal Phipps, Maureen G. TI Accuracy of Brief Screening Tools for Identifying Postpartum Depression Among Adolescent Mothers SO PEDIATRICS LA English DT Article DE teenage; pregnancy; screening; postpartum depression; validity ID WELL-CHILD VISITS; POSTNATAL DEPRESSION; MATERNAL DEPRESSION; SOCIAL SUPPORT; SYMPTOMS; INSTRUMENTS; VALIDITY; SCALE; VALIDATION; MANAGEMENT AB OBJECTIVE: To evaluate the accuracy of the Edinburgh Postnatal Depression Scale (EPDS) and 3 subscales for identifying postpartum depression among primiparous adolescent mothers. METHODS: Mothers enrolled in a randomized controlled trial to prevent postpartum depression completed a psychiatric diagnostic interview and the 10-item EPDS at 6 weeks, 3 months, and 6 months postpartum. Three subscales of the EPDS were assessed as brief screening tools: 3-item anxiety subscale (EPDS-3), 7-item depressive symptoms subscale (EPDS-7), and 2-item subscale (EPDS-2) that resemble the Patient Health Questionnaire-2. Receiver operating characteristic curves and the areas under the curves for each tool were compared to assess accuracy. The sensitivities and specificities of each screening tool were calculated in comparison with diagnostic criteria for a major depressive disorder. Repeated-measures longitudinal analytical techniques were used. RESULTS: A total of 106 women contributed 289 postpartum visits; 18% of the women met criteria for incident postpartum depression by psychiatric diagnostic interview. When used as continuous measures, the full EPDS, EPDS-7, and EPDS-2 performed equally well (area under the curve >0.9). Optimal cutoff scores for a positive depression screen for the EPDS and EPDS-7 were lower (>= 9 and >= 7, respectively) than currently recommended cutoff scores (>= 10). At optimal cutoff scores, the EPDS and EPDS-7 both had sensitivities of 90% and specificities of >85%. CONCLUSIONS: The EPDS, EPDS-7, and EPDS-2 are highly accurate at identifying postpartum depression among adolescent mothers. In primary care pediatric settings, the EPDS and its shorter subscales have potential for use as effective depression screening tools. C1 [Venkatesh, Kartik K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Venkatesh, Kartik K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Zlotnick, Caron; Phipps, Maureen G.] Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Zlotnick, Caron] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Zlotnick, Caron; Ware, Crystal; Phipps, Maureen G.] Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Providence, RI 02905 USA. [Triche, Elizabeth W.; Phipps, Maureen G.] Brown Univ, Dept Epidemiol, Program Publ Hlth, Providence, RI 02912 USA. RP Phipps, MG (reprint author), Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, 101 Dudley St, Providence, RI 02905 USA. EM mphipps@wihri.org RI Triche, Elizabeth/I-4986-2014 FU National Institute of Mental Health [R34MH77588]; National Institutes of Health (NIH) FX Supported by a grant from the National Institute of Mental Health (R34MH77588). Funded by the National Institutes of Health (NIH). NR 47 TC 10 Z9 13 U1 3 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2014 VL 133 IS 1 BP E45 EP E53 DI 10.1542/peds.2013-1628 PG 9 WC Pediatrics SC Pediatrics GA 282JX UT WOS:000329168400007 PM 24344102 ER PT J AU Bauer, MS Lee, A Li, MF Bajor, L Rasmusson, A Kazis, LE AF Bauer, Mark S. Lee, Austin Li, Mingfei Bajor, Laura Rasmusson, Ann Kazis, Lewis E. TI Off-label use of second generation antipsychotics for post-traumatic stress disorder in the Department of Veterans Affairs: time trends and sociodemographic, comorbidity, and regional correlates SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE antipsychotics; post-traumatic stress disorder; diffusion of innovations; pharmacoepidemiology ID TRAUMATIC BRAIN-INJURY; ADJUNCTIVE RISPERIDONE; PRESCRIPTION PATTERNS; PSYCHIATRIC-PATIENTS; TREAT SCHIZOPHRENIA; RACIAL DISPARITY; MEDICATION USE; UNITED-STATES; OPEN TRIAL; HEALTH AB PurposeSecond generation antipsychotics (SGAs) are widely used for post-traumatic stress disorder (PTSD), although without strong evidence base. With substantial numbers of veterans returning from Iraq/Afghanistan conflicts with PTSD, it is important to characterize the extent of SGA use and identify associated factors. MethodsWe determined time trends and patient characteristics associated with the use of SGAs in veterans with PTSD, without comorbid schizophrenia or bipolar disorders, using the Department of Veterans Affairs national administrative data 2003-2010. ResultsAmong 732085 veterans with PTSD, 27.6% received an intentional trial of an SGA in 2003-2010. The annual number treated with SGAs almost doubled (45268 to 84197, p<0.001), while prescribing rates decreased (28.6% to 21.5%, p<0.001). In multivariate analyses, African Americans (odds ratio (OR)=1.07, 95%confidence interval (CI)=1.06-1.09) and Hispanics (OR= 1.13, 95%CI=1.10-1.17) were more likely to receive SGAs than Whites. Strongest clinical associations were with prior diagnosis of depression (OR=1.96; 95%CI=1.94-1.99), substance use disorders (OR=1.86; 95%CI=1.84-1.88), and other anxiety disorders (OR=1.27; 95%CI=1.26-1.29) (all p-<0.0001) as well as cardiovascular risk factors. Veterans previously deployed to Iraq/Afghanistan had lower likelihood of SGA receipt. Substantial regional differences were demonstrated (South>Northeast; Midwest and West 0.05). Attendance and adherence rates to aerobic training were 82% and 66%, respectively. Intention-to-treat analysis indicated that VO2peak increased by 2.6 +/- 3.5 ml/kg/min (+ 13.3%) in the AC + AET group and decreased by 1.5 +/- 2.2 ml/kg/min (-8.6%) in the AC group (between group difference, p = 0.001). FACT-B increased 11.1 points in the AC + AET group compared to a 1.5 point decrease in the AC group (between group difference, p = 0.685). Conclusion. Moderate-to-high intensity aerobic training when conducted with one-on-one supervision is a safe adjunct therapy associated with improvements in cardiopulmonary function and select PROs during neoadjuvant chemotherapy. C1 [Hornsby, Whitney E.; Douglas, Pamela S.; West, Miranda J.; Kenjale, Aarti A.; Lane, Amy R.; Schwitzer, Emily R.; Herndon, James E., II; Hamilton, Erika; Kimmick, Gretchen G.; Peppercorn, Jeffrey M.; Jones, Lee W.] Duke Univ, Med Ctr, Durham, NC USA. [Ray, Kaitlin A.] Univ Tennessee, Med Ctr, Memphis, TN USA. [Coan, April] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Gutierrez, Antonio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hornsby, Kyle P.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Wilke, Lee G.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Jones, LW (reprint author), Duke Canc Inst, Box 3085, Durham, NC 27710 USA. EM lee.w.jones@duke.edu OI Sykes, April/0000-0002-7667-8155 FU United States Department of Defense Breast Cancer Research Program of the Office of the Congressionally Directed Medical Research Programs - Ideas Award; National Cancer Institute [CA143254, CA142566, CA138634, CA133895, CA164751] FX This study was supported by the United States Department of Defense Breast Cancer Research Program of the Office of the Congressionally Directed Medical Research Programs - Ideas Award and funds from George and Susan Beischer (LWJ). LWJ is supported by research grants from the National Cancer Institute (CA143254, CA142566, CA138634, CA133895, CA164751). NR 29 TC 23 Z9 23 U1 1 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0284-186X EI 1651-226X J9 ACTA ONCOL JI Acta Oncol. PD JAN PY 2014 VL 53 IS 1 BP 65 EP 74 DI 10.3109/0284186X.2013.781673 PG 10 WC Oncology SC Oncology GA 279FJ UT WOS:000328945500010 PM 23957716 ER PT J AU Bonn-Miller, MO Boden, MT Bucossi, MM Babson, KA AF Bonn-Miller, Marcel O. Boden, Matthew Tyler Bucossi, Meggan M. Babson, Kimberly A. TI Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Cannabis; marijuana; medical marijuana; strain; symptoms ID MARIJUANA USE MOTIVES; NATIONALLY REPRESENTATIVE SAMPLE; POSTTRAUMATIC-STRESS-DISORDER; USE COPING MOTIVES; CHRONIC PAIN; ANXIETY SENSITIVITY; SOCIAL ANXIETY; PANIC-ATTACKS; YOUNG-ADULTS; DEPENDENCE AB Objectives: Little research has investigated the demographic and symptom profile of medical cannabis users in states in the USA that have legalized cannabis use. Methods: In the present cross-sectional study, we investigated the demographic profile of 217 adults currently receiving medical cannabis, as well as differences in problematic use and perceived helpfulness in terms of (i) symptoms of psychological disorders and pain, and (ii) motives for use. Results: Findings indicated that medical cannabis users (i) use and perceive cannabis to be beneficial for multiple conditions, some for which cannabis is not specifically prescribed or allowed at the state level; and (ii) report similar rates of disordered use as compared with population estimates among regular users. Furthermore, problematic cannabis use was predicted by several symptoms of psychological disorders (e.g. depression) and a variety of use motives (e.g. coping), while cannabis was reported as particularly helpful among those with several psychological symptoms (e.g. traumatic intrusions), as well as those reporting use for social anxiety reasons. Conclusions: Results are discussed in terms of future directions for research given the current debates regarding legalization of cannabis for medical purposes and, more generally, the lack of empirical data to inform such debates. C1 [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.; Bucossi, Meggan M.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.; Boden, Matthew Tyler; Babson, Kimberly A.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Babson, Kimberly A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Bonn-Miller, MO (reprint author), VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA. EM marcel.bonn-miller@va.gov NR 67 TC 29 Z9 29 U1 0 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN PY 2014 VL 40 IS 1 BP 23 EP 30 DI 10.3109/00952990.2013.821477 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 279HL UT WOS:000328950900004 PM 24205805 ER PT J AU Bohnert, KM Walton, MA Resko, S Barry, KT Chermack, ST Zucker, RA Zimmerman, MA Booth, BM Blow, FC AF Bohnert, Kipling M. Walton, Maureen A. Resko, Stella Barry, Kristen T. Chermack, Stephen T. Zucker, Robert A. Zimmerman, Marc A. Booth, Brenda M. Blow, Frederic C. TI Latent class analysis of substance use among adolescents presenting to urban primary care clinics SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Adolescent health; latent class analysis; primary care; polysubstance use ID ALCOHOL-USE DISORDERS; DRUG-USE; CANNABIS USE; YOUNG ADULTHOOD; PREVENTION PROGRAM; PROTECTIVE FACTORS; POLYSUBSTANCE USE; ABUSE PREVENTION; UNITED-STATES; SELF-REPORT AB Background: Polysubstance use during adolescence is a significant public health concern. However, few studies have investigated patterns of substance use during this developmental window within the primary care setting. Objectives: This study used an empirical method to classify adolescents into substance use groups, and examines correlates of the empirically defined groups. Methods: Data came from patients, ages 12-18 years, presenting to an urban, primary care community health clinics (Federally Qualified Health Centers) in two cities in the Midwestern United States (n = 1664). Latent class analysis (LCA) was used to identify classes of substance users. Multinomial logistic regression was used to examine variables associated with class membership. Results: LCA identified three classes: class 1 (64.5%) exhibited low probabilities of all types of substance use; class 2 (24.6%) was characterized by high probabilities of cannabis use and consequences; and class 3 (10.9%) had the highest probabilities of substance use, including heavy episodic drinking and misuse of prescription drugs. Those in class 2 and class 3 were more likely to be older and have poorer grades, poorer health, higher levels of psychological distress and more sexual partners than those in class 1. Individuals in class 3 were also less likely to be African-American than those in class 1. Conclusion: Findings provide novel insight into the patterns of substance use among adolescents presenting to low-income urban primary care clinics. Future research should examine the efficacy of interventions that address the complex patterns of substance use and concomitant health concerns among adolescents. C1 [Bohnert, Kipling M.; Barry, Kristen T.; Chermack, Stephen T.; Blow, Frederic C.] US Dept Vet Affairs, Natl Serious Mental Illness Treatment Resource &, Ann Arbor, MI USA. [Bohnert, Kipling M.; Walton, Maureen A.; Barry, Kristen T.; Chermack, Stephen T.; Zucker, Robert A.; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Resko, Stella] Wayne State Univ, Sch Social Work, Detroit, MI USA. [Resko, Stella] Wayne State Univ, Merrill Palmer Skillman Inst, Detroit, MI USA. [Zimmerman, Marc A.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Booth, Brenda M.] US Dept Vet Affairs, Ctr Mental Hlth Outcomes & Res, Little Rock, AR USA. [Booth, Brenda M.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RP Bohnert, KM (reprint author), NCRC, 2800 Plymouth Rd Bldg 16,Rm 243E, Ann Arbor, MI 48109 USA. EM kiplingb@med.umich.edu FU NIDA NIH HHS [DA020075, R01 DA020075] NR 58 TC 9 Z9 9 U1 4 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN PY 2014 VL 40 IS 1 BP 44 EP 50 DI 10.3109/00952990.2013.844821 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 279HL UT WOS:000328950900007 PM 24219231 ER PT J AU Mojta, C Falconier, MK Huebner, AJ AF Mojta, Carl Falconier, Mariana K. Huebner, Angela J. TI Fostering Self-Awareness in Novice Therapists Using Internal Family Systems Therapy SO AMERICAN JOURNAL OF FAMILY THERAPY LA English DT Article AB This qualitative study used a phenomenological approach to understand: (a) whether and how the Internal Family Systems (IFS) model helps beginning therapists gain awareness of their internal processes and (b) whether and how such awareness influences their clinical work. Semi-structured individual interviews were conducted with seven beginning therapists and data were analyzed using thematic coding. Findings suggest that IFS helped therapists identify, understand, and manage their internal processes, which seemed to benefit the therapeutic relationship, identify therapists' personal agendas, model work with the internal system, and foster a better understanding of the client's internal system. Clinical training implications are discussed. C1 [Mojta, Carl] US Dept Vet Affairs, Readjustment Counseling Serv, DC Vet Ctr, Washington, DC USA. [Falconier, Mariana K.; Huebner, Angela J.] Virginia Polytech Inst & State Univ, Dept Human Dev, Falls Church, VA 22043 USA. RP Falconier, MK (reprint author), Virginia Polytech Inst & State Univ, Dept Human Dev, 7054 Haycock Rd,Suite 202C, Falls Church, VA 22043 USA. EM marianak@vt.edu NR 22 TC 1 Z9 1 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0192-6187 EI 1521-0383 J9 AM J FAM THER JI Am. J. Fam. Ther. PD JAN 1 PY 2014 VL 42 IS 1 BP 67 EP 78 DI 10.1080/01926187.2013.772870 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 281ZC UT WOS:000329138800006 ER PT J AU Evans, ME Kralovic, SM Simbartl, LA Freyberg, RW Obrosky, DS Roselle, GA Jain, R AF Evans, Martin E. Kralovic, Stephen M. Simbartl, Loretta A. Freyberg, Ron W. Obrosky, D. Scott Roselle, Gary A. Jain, Rajiv TI Nationwide reduction of health careeassociated methicillin-resistant Staphylococcus aureus infections in Veterans Affairs long-term care facilities SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Methicillin-resistant Staphylococcus aureus; Long-term care; Nursing home; Health care-associated infection ID NURSING-HOMES; COLONIZATION; PREVENTION; RESIDENTS; CARRIAGE AB The Veterans Affairs methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative was implemented in its 133 long-term care facilities in January 2009. Between July 2009 and December 2012, there were similar to 12.9 million resident-days in these facilities nationwide. During this period, the mean quarterly MRSA admission prevalence increased from 23.3% to 28.7% (P < .0001, Poisson regression for trend), but the overall rate of MRSA health care-associated infections decreased by 36%, from 0.25 to 0.16/1,000 resident-days (P < .0001, Poisson regression for trend). Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Evans, Martin E.] Vet Hlth Adm MRSA, MDRO Program Off, Vet Affairs Cent Off, Natl Infect Dis Serv,Patient Care Serv, Lexington, KY USA. [Evans, Martin E.] Lexington Vet Affairs Med Ctr, Lexington, KY USA. [Evans, Martin E.] Univ Kentucky, Sch Med, Dept Internal Med, Lexington, KY 40536 USA. [Kralovic, Stephen M.; Simbartl, Loretta A.; Roselle, Gary A.] Vet Affairs Cent Off, Patient Care Serv, Natl Infect Dis Serv, Cincinnati, OH USA. [Kralovic, Stephen M.; Simbartl, Loretta A.; Roselle, Gary A.] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. [Kralovic, Stephen M.; Roselle, Gary A.] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH USA. [Freyberg, Ron W.] Vet Affairs Inpatient Evaluat Ctr, Cincinnati, OH USA. [Obrosky, D. Scott] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Vet Affairs Cent Off, Patient Care Serv, Washington, DC USA. RP Evans, ME (reprint author), 1101 Vet Dr, Lexington, KY 40502 USA. EM Martin.Evans@va.gov NR 13 TC 13 Z9 13 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD JAN PY 2014 VL 42 IS 1 BP 60 EP 62 DI 10.1016/j.ajic.2013.06.004 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 282IT UT WOS:000329165200015 PM 24388470 ER PT J AU O'Seaghdha, CM Tin, A Yang, Q Katz, R Liu, YM Harris, T Astor, B Coresh, J Fox, CS Kao, WHL Shlipak, MG AF O'Seaghdha, Conall M. Tin, Adrienne Yang, Qiong Katz, Ronit Liu, YongMei Harris, Tamara Astor, Brad Coresh, Josef Fox, Caroline S. Kao, W. H. Linda Shlipak, Michael G. TI Association of a Cystatin C Gene Variant With Cystatin C Levels, CKD, and Risk of Incident Cardiovascular Disease and Mortality SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Cystatin C; chronic kidney disease; genetics; single-nucleotide polymorphism; net reclassification improvement ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; GENOME-WIDE ASSOCIATION; SERUM CREATININE; ELDERLY PERSONS; POOLED ANALYSIS; RENAL-DISEASE; EQUATION; RECLASSIFICATION; PREDICTION AB Background: Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFR(cys)). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality. Study Design: Observational. Setting&Population: 4 population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Composition (Health ABC) studies. Predictors: We estimated the association of rs13038305 with eGFR(cys) and serum creatinine-based eGFR (eGFR(cr)) and performed longitudinal analyses of the associations of eGFR(cys) with mortality and cardiovascular events following adjustment for rs13038305. Outcomes: We assessed reclassification by genotype-adjusted eGFR(cys) across CKD categories:, 45, 45-59, 60-89, and >= 90mL/min/1.73m(2). We compared mortality and CVD outcomes in those reclassified to a worse eGFR(cys) category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis. Results: In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21%) was associated with a 6.4% lower cystatin C concentration, 5.5-mL/min/1.73m(2) higher eGFR(cys), and 36%[95% CI, 29%-41%] lower odds of CKD. Associations with CVD (HR, 1.17; 95% CI, 1.14-1.20) and mortality (HR, 1.22; 95% CI, 1.19-1.24) per 10-mL/min/1.73m(2) lower eGFR(cys) were similar with or without rs13038305 adjustment. 1,134 (7.7%) participants were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95% CI, 20.003 to 0.022) for mortality and 0.014 (95% CI, 0.0 to 0.028) for CVD. Limitations: rs13038305 explains only a small proportion of cystatin C variation. Conclusions: Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Tin, Adrienne; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Katz, Ronit; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Katz, Ronit; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Liu, YongMei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Harris, Tamara] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. [Astor, Brad] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, 4150 Clement St 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu RI Yang, Qiong/G-5438-2014 FU National Institute on Aging (NIA) [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Institutes of Health (NIH) [HHSN268200782096C]; Intramural Research Program of the NIH, NIA FX Support: This research was supported by National Institute on Aging (NIA) contracts N01AG62101, N01AG62103, and N01AG62106. The GWAS was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University, contract HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, NIA. NR 24 TC 6 Z9 6 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2014 VL 63 IS 1 BP 16 EP 22 DI 10.1053/j.ajkd.2013.06.015 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 281PA UT WOS:000329112300007 PM 23932088 ER PT J AU Kohli, P Steg, PG Cannon, CP Smith, SC Eagle, KA Ohman, EM Alberts, MJ Hoffman, E Guo, JP Simon, T Sorbets, E Goto, S Bhatt, DL AF Kohli, Payal Steg, Ph. Gabriel Cannon, Christopher P. Smith, Sidney C., Jr. Eagle, Kim A. Ohman, E. Magnus Alberts, Mark J. Hoffman, Elaine Guo, Jianping Simon, Tabassome Sorbets, Emmanuel Goto, Shinya Bhatt, Deepak L. CA REACH Registry Investigators TI NSAID Use and Association with Cardiovascular Outcomes in Outpatients with Stable Atherothrombotic Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Heart failure; NSAID; Outcomes; Stable atherothrombosis ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; EVENT RATES; CYCLOOXYGENASE-2 INHIBITORS; NATIONWIDE COHORT; BLOOD-PRESSURE; RISK; METAANALYSIS; POPULATION AB BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin have been linked to heart failure, salt retention, adverse ventricular remodeling, and thrombosis. We therefore sought to assess their impact on cardiovascular events in outpatients with stable atherothrombotic disease. METHODS: We analyzed 44,095 patients in the REduction of Atherothrombosis for Continued Health (REACH) registry with information on NSAID use and 4-year follow-up. Cox proportional hazard models, including NSAID use as a time-dependent covariate, were constructed and adjusted for key baseline characteristics. End points of interest included multivariate adjusted: cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations; cardiovascular death/myocardial infarction/stroke; hospitalization for heart failure; and individual components of the composite end points. RESULTS: Compared with NSAID nonusers (n = 39,675), NSAID users (n = 4420) were older (70 vs 68 years), more frequently female and white, and had more baseline heart failure and atherosclerotic risk factors (hypertension, dyslipidemia, diabetes, reduced creatinine clearance) (all P <.001). NSAID use was associated with an increased hazard for cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations (adjusted hazard ratio [adj. HR] 1.12; 95% confidence interval [CI], 1.04-1.21; P = .003) and for cardiovascular death/myocardial infarction/stroke (adj. HR 1.16; 95% CI, 1.03-1.30; P = .02). There also was a higher risk of myocardial infarction (adj. HR 1.37; 95% CI, 1.12-1.68; P = .002), stroke (adj. HR 1.21; 95% CI, 1.00-1.45; P = .048), heart failure hospitalizations (adj. HR 1.18; 95% CI, 1.03-1.34; P = .013), and ischemic hospitalizations (adj. HR 1.17; 95% CI, 1.07-1.27; P = .001). CONCLUSION: Among patients with stable atherothrombosis, NSAID use is associated with a higher risk of myocardial infarction, stroke, and hospitalizations for both ischemia and heart failure. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kohli, Payal] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Kohli, Payal; Sorbets, Emmanuel] Univ Paris Diderot, Hop Bichat, AP HP, Sorbonne Paris Cite, Paris, France. [Steg, Ph. Gabriel; Simon, Tabassome; Sorbets, Emmanuel] INSERM, U698, Paris, France. [Cannon, Christopher P.; Hoffman, Elaine; Guo, Jianping; Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Smith, Sidney C., Jr.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ohman, E. Magnus] Duke Clin Res Inst, Durham, NC USA. [Alberts, Mark J.] Univ Texas Southwestern, Dallas, TX USA. [Simon, Tabassome] URCEST, Hop St Antoine, AP HP, Paris, France. [Simon, Tabassome] UPMC Paris 06, Paris, France. [Goto, Shinya] Tokai Univ, Hiratsuka, Kanagawa 25912, Japan. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu FU Sanofi Aventis; Bristol-Myers Squibb; Waksman Foundation FX The REduction of Atherothrombosis for Continued Health (REACH) study was sponsored by Sanofi Aventis, Bristol-Myers Squibb, and the Waksman Foundation and is endorsed by the World Heart Federation. NR 36 TC 10 Z9 10 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2014 VL 127 IS 1 BP 53 EP + DI 10.1016/j.amjmed.2013.08.017 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 281UA UT WOS:000329125300022 PM 24280110 ER PT J AU Little, BP Gilman, MD Humphrey, KL Alkasab, TK Gibbons, FK Shepard, JAO Wu, CC AF Little, Brent P. Gilman, Matthew D. Humphrey, Kathryn L. Alkasab, Tarik K. Gibbons, Fiona K. Shepard, Jo-Anne O. Wu, Carol C. TI Outcome of Recommendations for Radiographic Follow-Up of Pneumonia on Outpatient Chest Radiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest radiography; community-acquired pneumonia; lung cancer ID COMMUNITY-ACQUIRED PNEUMONIA; NONRESOLVING PNEUMONIA; LUNG-CANCER; MANAGEMENT; DIAGNOSIS; GUIDELINES; SOCIETY; ADULTS AB OBJECTIVE. Follow-up chest radiographs are frequently recommended by radiologists to document the clearing of radiographically suspected pneumonia. However, the clinical utility of follow-up radiography is not well understood. The purpose of this study was to examine the incidence of important pulmonary pathology revealed during follow-up imaging of suspected pneumonia on outpatient chest radiography. MATERIALS AND METHODS. Reports of 29,138 outpatient chest radiography examinations performed at an academic medical center in 2008 were searched to identify cases in which the radiologist recommended follow-up chest radiography for presumed community-acquired pneumonia (n = 618). Descriptions of index radiographic abnormalities were recorded. Reports of follow-up imaging (radiography and CT) performed during the period from January 2008 to January 2010 were reviewed to assess the outcome of the index abnormality. Clinical history, demographics, microbiology, and pathology reports were reviewed and recorded. RESULTS. Compliance with follow-up imaging recommendations was 76.7%. In nine of 618 cases (1.5%), a newly diagnosed malignancy corresponded to the abnormality on chest radiography initially suspected to be pneumonia. In 23 of 618 cases (3.7%), an alternative nonmalignant disease corresponded with the abnormality on chest radiography initially suspected to be pneumonia. Therefore, in 32 of 618 patients (5.2%), significant new pulmonary diagnoses were established during follow-up imaging of suspected pneumonia. CONCLUSION. Follow-up imaging of radiographically suspected pneumonia leads to a small number of new diagnoses of malignancy and important nonmalignant diseases, which may alter patient management. C1 [Little, Brent P.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Gilman, Matthew D.; Humphrey, Kathryn L.; Alkasab, Tarik K.; Shepard, Jo-Anne O.; Wu, Carol C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Gibbons, Fiona K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pulm & Crit Care Unit, Boston, MA USA. RP Wu, CC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM carolcwu@gmail.com NR 14 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2014 VL 202 IS 1 BP 54 EP 59 DI 10.2214/AJR.13.10888 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 281PH UT WOS:000329113000025 PM 24370128 ER PT J AU Niell, BL Lee, JM Johansen, C Halpern, EF Rafferty, EA AF Niell, Bethany L. Lee, Janie M. Johansen, Christopher Halpern, Elkan F. Rafferty, Elizabeth A. TI Patient Outcomes in Canceled MRI-Guided Breast Biopsies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; breast MRI; MRI-guided biopsy; MRI-guided intervention ID CONTRAST-MEDIUM; FOLLOW-UP; ENHANCEMENT; ULTRASOUND; WOMEN AB OBJECTIVE. The reported frequency of aborted MRI-guided breast biopsies ranges from 8% to 17%, usually secondary to nonvisualization at attempted biopsy. Our study examines the frequency of MRI-guided breast biopsies aborted because of lesion nonvisualization and the subsequent risk of malignancy. MATERIALS AND METHODS. We identified 350 patients and 445 lesions scheduled for MRI-guided biopsy between January 1, 2007, and December 31, 2009. Medical records and imaging studies were reviewed to ascertain patient demographics, lesion and imaging characteristics, and subsequent pathology results. Chi-square statistics were calculated for patient level analyses. RESULTS. MRI-guided biopsies were aborted in 13% (56/445) of lesions and 15% (53/350; 95% CI, 11.6-19.3%) of patients because of nonvisualization of the biopsy target at the time of attempted biopsy. Of these 53 patients, 50 patients had follow-up data available. Malignancy was subsequently diagnosed in five of those 50 patients (10%; 95% CI, 3.321.8%), three with invasive ductal carcinomas and two with ductal carcinoma in situ. The mean time to malignant diagnosis from the date of aborted biopsy was 2.6 months (range, 1.1-6.9 months). CONCLUSION. Informed consent for MRI-guided breast biopsies should include discussion of biopsy cancellation because of nonvisualization of the target lesion. The low yet significant risk of malignancy in patients subsequent to an aborted MRI-guided breast biopsy warrants short-term follow-up MRI after a canceled biopsy. C1 [Niell, Bethany L.; Lee, Janie M.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Johansen, Christopher] Kingman Reg Med Ctr, Dept Radiol, Kingman, AZ USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Niell, BL (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, 55 Fruit St,Wang Bldg,Ste 240, Boston, MA 02114 USA. EM bniell@partners.org FU NCI NIH HHS [K07 CA128816] NR 15 TC 2 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2014 VL 202 IS 1 BP 223 EP 228 DI 10.2214/AJR.12.10228 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 281PH UT WOS:000329113000046 PM 24370148 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Disability as a covariate in risk adjustment models for predicting hospital deaths SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Disability; Hospital mortality; Risk adjustment ID PERCUTANEOUS CORONARY INTERVENTION; PROSPECTIVE-PAYMENT SYSTEM; NEW-YORK-STATE; ACUTE MYOCARDIAL-INFARCTION; CARDIAC-SURGERY; FUNCTIONAL STATUS; CLASSIFICATION-SYSTEM; MORTALITY-RATES; WIDE MORTALITY; SURGICAL CARE AB Risk-adjusted hospital mortality rates are frequently used as putative indicators of hospital quality. These figures could become increasingly important as efforts escalate to contain U.S. health care costs while simultaneously maintaining or improving quality of care. Most risk adjustment methods today employ coded diagnostic information sometimes supplemented with more detailed clinical data obtained from medical records. This article considers whether risk-adjusted hospital mortality rates should account for baseline patient disability. Accounting for baseline disability when calculating hospital mortality rates makes clinical sense, especially for conditions such as heart failure or coronary artery bypass grafting surgery, where patients' cardiac-related functional status strongly predicts their imminent outcomes. A small body of research suggests the strength of disability in predicting hospital mortality, even in comparison with indicators of acute physiologic status and comorbid illness. However, the feasibility of obtaining complete and accurate data on patients' baseline disability will be challenging and requires further investigation. The risk of not adjusting for baseline disability could be efforts by physicians and hospitals to avoid treating patients with significant disabilities. (C) 2014 Elsevier Inc. All rights reserved. C1 [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Mongan Inst Hlth Policy, Boston, MA USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org NR 51 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2014 VL 24 IS 1 BP 17 EP 22 DI 10.1016/j.annepidem.2013.10.016 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 280AR UT WOS:000329001500004 PM 24262999 ER PT J AU Salata, MJ Bailey, JR Bell, R Frank, RM McGill, KC Lin, EC Kercher, JS Wang, VM Provencher, MT Mazzocca, AD Verma, NN Romeo, AA AF Salata, Michael J. Bailey, James R. Bell, Rebecca Frank, Rachel M. McGill, Kevin C. Lin, Emery C. Kercher, James S. Wang, Vincent M. Provencher, Matthew T. Mazzocca, Augustus D. Verma, Nikhil N. Romeo, Anthony A. TI Effect of Interference Screw Depth on Fixation Strength in Biceps Tenodesis SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID SUTURE ANCHOR FIXATION; ROTATOR CUFF TEARS; LONG-HEAD; BIOMECHANICAL EVALUATION; TENDON; MANAGEMENT; TENOTOMY; BRACHII; TENDINOPATHY; DIAGNOSIS AB The purpose of this study was to assess the biomechanical performance of the long head of the biceps tenodesis with an interference screw with respect to screw depth. Methods: Twenty-one human cadaveric shoulders were randomized into 3 treatment groups (7 each): interference screw placed flush to the humeral cortex, 50% proud, or fully recessed. Bone density was determined, and subpectoral biceps tenodesis was performed with 8 x 12 mm Bio-Tenodesis screws (Arthrex, Naples, FL). Each construct was cyclically loaded from 5 to 70 N for 500 cycles at 1 Hz and then pulled to failure at 1 mm/s. Relative actuator displacement was calculated from cyclic testing. Maximum load, elongation, linear stiffness, and failure mode were recorded from pull-to-failure testing. Because of numerous failures during cyclic testing, the final load data from the fully recessed group were not statistically analyzed. The remaining groups were compared by use of a 2-tailed, Student unpaired t test and chi(2) analysis. Results: There was no significant difference in displacement among groups during cyclic testing. Five specimens in the recessed group failed during cyclic testing, whereas 2 specimens and 0 specimens failed in the proud and flush groups, respectively. The maximum loads sustained were 281.6 +/- 77.8 N, 184.5 +/- 56.3 N, and 209.1 +/- 57.0 N for the flush group, 50% proud group, and recessed group (in those specimens surviving cyclical loading), respectively. Conclusions: Placement of a Bio-Tenodesis screw flush to the humeral cortex is preferred for maximum fixation strength in subpectoral biceps tenodesis. A screw placed to 50% depth may be effective in the laboratory setting, but recessed placement is more variable and requires additional fixation. The fully recessed group resulted in 5 of 7 failures during cyclical loading, with no specimens failing in the flush group. Clinical Relevance: This study shows the importance of determining the optimal depth of interference screw placement during biceps tenodesis to obtain optimal biomechanical performance and reduce the risk of fixation failure. C1 [Salata, Michael J.; Bell, Rebecca; Frank, Rachel M.; McGill, Kevin C.; Lin, Emery C.; Kercher, James S.; Wang, Vincent M.; Verma, Nikhil N.; Romeo, Anthony A.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Bailey, James R.] Naval Med Ctr, Dept Orthopaed Surg, San Diego, CA USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Mazzocca, Augustus D.] Univ Connecticut, Ctr Hlth, Dept Orthopaed Surg, Farmington, CT USA. RP Verma, NN (reprint author), Rush Univ, Med Ctr, 1611 W Harrison St, Chicago, IL 60612 USA. EM nverma@rushortho.com OI Romeo, Anthony/0000-0003-4848-3411 FU Objective Medical Assessments; Arthrex; Major League Baseball; owns stock in Omeros; DJO Surgical; Joint Restoration Foundation FX The authors report the following potential conflict of interest or source of funding: M.T.P. receives support from Objective Medical Assessments. A.D.M. is a consultant for and has received research support from Arthrex. N.N.V. is on the Smith & Nephew Shoulder Advisory Board and the Board of Vindico Medical, is a consultant for Smith & Nephew, has received grants from Major League Baseball, and owns stock in Omeros. A.A.R. is a consultant for Arthrex, and has received support from Major League Baseball, DJO Surgical, and Joint Restoration Foundation. NR 31 TC 5 Z9 5 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD JAN PY 2014 VL 30 IS 1 BP 11 EP 15 DI 10.1016/j.arthro.2013.08.033 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 282IH UT WOS:000329164000006 PM 24183106 ER PT J AU Frank, RM Erickson, B Frank, JM Bush-Joseph, CA Bach, BR Cole, BJ Romeo, AA Provencher, MT Verma, NN AF Frank, Rachel M. Erickson, Brandon Frank, Jonathan M. Bush-Joseph, Charles A. Bach, Bernard R., Jr. Cole, Brian J. Romeo, Anthony A. Provencher, Matthew T. Verma, Nikhil N. TI Utility of Modern Arthroscopic Simulator Training Models SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Review ID VIRTUAL-REALITY SIMULATOR; SHOULDER ARTHROSCOPY; ORTHOPEDIC-SURGERY; OPERATING-ROOM; SKILLS; PERFORMANCE; PROFICIENCY; WORK; KNEE; EXPERIENCE AB Purpose: The purpose of this study was to review the published literature on modern arthroscopic simulator training models to (1) determine the ability to transfer skills learned on the model to the operating room and (2) determine the learning curve required to translate such skills. Methods: A systematic review of all studies using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed. Two independent reviewers then analyzed studies deemed appropriate for inclusion. Study data collected included participant demographic characteristics, simulator model, type and number of tasks, method of analysis, and results of training, when available. Given the different methods used in each study, descriptive analysis was performed. Results: Nineteen studies met the inclusion criteria (9 shoulder, 9 knee, and 1 hip). A total of 465 participants with a mean age of 30 years were evaluated. Twelve studies (63%) compared task performance among participants of different experience levels, with 100% reporting a positive correlation between experience level and simulator performance. Eight studies (42%) evaluated task performance before and after simulator training, with 6 studies showing improvement after training; 1 study noted no difference in performance after 1 hour of training. One study commented on improved operating room performance after simulator training. No studies commented on the number of training sessions needed to translate skills learned on the models to the operating room. Conclusions: This review suggests that practice on arthroscopic simulators improves performance on arthroscopic simulators. We cannot, however, definitively comment on whether simulator training correlates to an improved skill set in the operating room. Further work is needed to determine the type and number of training sessions needed to translate arthroscopic skills learned on the models to the operating room. Level of Evidence: Level IV, systematic review of studies with Level I through IV evidence. C1 [Frank, Rachel M.; Erickson, Brandon; Frank, Jonathan M.; Bush-Joseph, Charles A.; Bach, Bernard R., Jr.; Cole, Brian J.; Romeo, Anthony A.; Verma, Nikhil N.] Rush Univ, Med Ctr, Rush Med Coll, Div Sports Med,Dept Orthopaed Surg, Chicago, IL 60612 USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Frank, RM (reprint author), Rush Univ, Med Ctr, 1611 W Harrison St, Chicago, IL 60612 USA. EM rmfrank3@gmail.com OI Romeo, Anthony/0000-0003-4848-3411 NR 45 TC 27 Z9 27 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD JAN PY 2014 VL 30 IS 1 BP 121 EP 133 DI 10.1016/j.arthro.2013.09.084 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 282IH UT WOS:000329164000022 PM 24290789 ER PT J AU Shafi, MM Westover, MB Oberman, L Cash, SS Pascual-Leone, A AF Shafi, Mouhsin M. Westover, M. Brandon Oberman, Lindsay Cash, Sydney S. Pascual-Leone, Alvaro TI Modulation of EEG Functional Connectivity Networks in Subjects Undergoing Repetitive Transcranial Magnetic Stimulation SO BRAIN TOPOGRAPHY LA English DT Article DE TMS; EEG; Resting state; Networks; Functional connectivity; Graph theory ID HUMAN MOTOR CORTEX; GRAPH-THEORETICAL ANALYSIS; THETA-BURST-STIMULATION; SMALL-WORLD NETWORKS; HIGH-FREQUENCY; CORTICAL NETWORKS; HUMAN BRAIN; MULTIPLE-SCLEROSIS; COMPLEX NETWORKS; ALPHA-FREQUENCY AB Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that utilizes magnetic fluxes to alter cortical activity. Continuous theta-burst repetitive TMS (cTBS) results in long-lasting decreases in indices of cortical excitability, and alterations in performance of behavioral tasks. We investigated the effects of cTBS on cortical function via functional connectivity and graph theoretical analysis of EEG data. Thirty-one channel resting-state EEG recordings were obtained before and after 40 s of cTBS stimulation to the left primary motor cortex. Functional connectivity between nodes was assessed in multiple frequency bands using lagged max-covariance, and subsequently thresholded to construct undirected graphs. After cTBS, we find widespread decreases in functional connectivity in the alpha band. There are also simultaneous increases in functional connectivity in the high-beta bands, especially amongst anterior and interhemispheric connections. The analysis of the undirected graphs reveals that interhemispheric and interregional connections are more likely to be modulated after cTBS than local connections. There is also a shift in the topology of network connectivity, with an increase in the clustering coefficient after cTBS in the beta bands, and a decrease in clustering and increase in path length in the alpha band, with the alpha-band connectivity primarily decreased near the site of stimulation. cTBS produces widespread alterations in cortical functional connectivity, with resulting shifts in cortical network topology. C1 [Shafi, Mouhsin M.; Westover, M. Brandon; Oberman, Lindsay; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Dept Neurol, Div Cognit Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Shafi, Mouhsin M.] Beth Israel Deaconess Med Ctr, Dept Neurol, Epilepsy Serv, Boston, MA 02215 USA. [Shafi, Mouhsin M.; Westover, M. Brandon; Cash, Sydney S.; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Westover, M. Brandon; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Univ Neurorehabil Guttmann, Badalona, Spain. RP Shafi, MM (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Div Cognit Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, 330 Brookline Ave, Boston, MA 02215 USA. EM mouhsin.shafi@gmail.com FU National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758]; Center for Integration of Medicine and Innovative Technology (CIMIT); Sidney R. Baer, Jr. Foundation; Nexstim; NIH/NINDS [RO1-NS062092]; NIH fellowship [F32MH080493, 1KL2RR025757-01] FX Work on this study was supported by grants from the National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758), Center for Integration of Medicine and Innovative Technology (CIMIT), the Sidney R. Baer, Jr. Foundation, and Nexstim to APL. MMS was supported by funds from the National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758), and the Center for Integration of Medicine and Innovative Technology (CIMIT). MBW and SSC receive research support from the NIH/NINDS (RO1-NS062092). LO was supported by NIH fellowship F32MH080493 and 1KL2RR025757-01. NR 86 TC 10 Z9 10 U1 2 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0896-0267 EI 1573-6792 J9 BRAIN TOPOGR JI Brain Topogr. PD JAN PY 2014 VL 27 IS 1 BP 172 EP 191 DI 10.1007/s10548-013-0277-y PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 283DV UT WOS:000329226500017 PM 23471637 ER PT J AU Gardner, A Iverson, GL McCrory, P AF Gardner, Andrew Iverson, Grant L. McCrory, Paul TI Chronic traumatic encephalopathy in sport: a systematic review SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Review DE Concussion; Neurology; Sporting injuries; Trauma surgery; Head injuries ID NATIONAL-FOOTBALL-LEAGUE; METABOLIC BRAIN VULNERABILITY; REPETITIVE HEAD-INJURY; COGNITIVE IMPAIRMENT; RECURRENT CONCUSSION; TEMPORAL WINDOW; PLAYERS; DEMENTIA; DEPRESSION; BIOMARKERS AB Objective To provide a critical review of chronic traumatic encephalopathy (CTE) by considering the range of clinical presentations, neuropathology and the strength of evidence for CTE as a distinct syndrome. Data sources Seven electronic databases were searched using a combination of MeSH terms and key words to identify relevant articles. Review methods Specific inclusion and exclusion criteria were used to select studies for review. Data extracted where present included study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, investigation results and neuropathology results. Results The data from 158 published case studies were reviewed. Critical differences between the older descriptions of CTE (the classic' syndrome) and the recent descriptions (the modern' syndrome) exist in the age of onset, natural history, clinical features, pathological findings and diagnostic criteria, which suggests that modern CTE is a different syndrome. The methodology of the current studies does not allow determination of aetiology or risk factors. Conclusions The clinicopathological differences between the classic' CTE syndrome and the modern' syndrome suggest that the new syndrome needs a different nomenclature. Further research is required to clearly define the clinical phenotype of the modern CTE syndrome and establish the underlying aetiology. Future research needs to address these issues through large-scale, prospective clinicopathological studies. C1 [Gardner, Andrew] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [McCrory, Paul] Melbourne Brain Ctr, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. RP Gardner, A (reprint author), Calvary Mater Hosp, Ctr Translat Neurosci & Mental Hlth, Level 5,McAuley Bldg, Waratah, NSW 2298, Australia. EM andrew.gardner@neurogard.com.au RI Gardner, Andrew/J-5162-2013 FU Victorian Government; Operational Infrastructure Support Grant. FX The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. NR 65 TC 57 Z9 57 U1 10 U2 46 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD JAN PY 2014 VL 48 IS 2 BP 84 EP U88 DI 10.1136/bjsports-2013-092646 PG 8 WC Sport Sciences SC Sport Sciences GA 276KK UT WOS:000328749000007 PM 23803602 ER PT J AU Raymond, E Dalgleish, A Damber, JE Smith, M Pili, R AF Raymond, E. Dalgleish, A. Damber, J. -E. Smith, M. Pili, R. TI Mechanisms of action of tasquinimod on the tumour microenvironment SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Review DE Tasquinimod; Quinoline carboxamide; Tumour microenvironment; Myeloid-derived suppressor cell; Tumour-associated macrophage; S100A9 ID RESISTANT PROSTATE-CANCER; HISTONE DEACETYLASE INHIBITORS; CHRONIC IMMUNE ACTIVATION; ANTI-ANGIOGENIC AGENT; SUPPRESSOR-CELLS; S100A9; INFLAMMATION; METASTASIS; THROMBOSPONDIN-1; EXPRESSION AB Tasquinimod is a small molecule with pleiotropic effects on the tumour microenvironment. Tasquinimod inhibits the growth and metastasis of tumour cells in vitro and in vivo. It targets the tumour microenvironment, enhancing the host immune response and inhibiting the angiogenic response. Tasquinimod influences infiltrating myeloid cells in the tumour milieu shifting the balance towards a less immunosuppressive phenotype. Myeloid-derived suppressor cells and tumour-associated macrophages are major components of the immunosuppressive microenvironment and as a result promote tumour growth and favour angiogenesis and metastasis formation. Growing evidence indicates that tasquinimod targets these myeloid cells and modulates local tumour immunity by blocking the interaction between the multifunctional protein S100A9 and its ligands receptor of advanced glycation end products and Toll-like receptor 4. Its anti-angiogenic effects are achieved at least in part through these effects on regulatory myeloid cells and also potentially through inactivating histone deacetylase-4 and reducing expression of hypoxia-inducible factor 1-controlled genes. The aim is to comprehensively review the mode of action of tasquinimod as a novel oral anti-cancer agent. Based on its unique combination of effects, tasquinimod is a novel agent with clinical therapeutic potential in various solid tumours, both alone and as part of rational combination therapy. C1 [Raymond, E.] Beaujon Univ Hosp, Dept Med Oncol, Clichy, France. [Raymond, E.] Hop Beaujon, Serv Cancerol, F-92110 Clichy, France. [Dalgleish, A.] Univ London, Dept Oncol, Div Cellular & Mol Med, London, England. [Damber, J. -E.] Gothenburg Univ, Inst Clin Sci, Dept Urol, Gothenburg, Sweden. [Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Pili, R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Raymond, E (reprint author), Beaujon Univ Hosp, Dept Med Oncol, Clichy, France. EM eric.raymond@bjn.aphp.fr FU Ipsen FX This paper is based on the discussions at a meeting held in September 2012 funded by Ipsen. Editorial assistance in the development of this manuscript was provided by Christine Drewienkiewicz of Choice Healthcare Solutions and funded by Ipsen. NR 61 TC 19 Z9 19 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2014 VL 73 IS 1 BP 1 EP 8 DI 10.1007/s00280-013-2321-8 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 283CU UT WOS:000329223200001 PM 24162378 ER PT J AU Harmon, CS DePrimo, SE Figlin, RA Hudes, GR Hutson, TE Michaelson, MD Negrier, S Kim, ST Huang, X Williams, JA Eisen, T Motzer, RJ AF Harmon, Charles S. DePrimo, Samuel E. Figlin, Robert A. Hudes, Gary R. Hutson, Thomas E. Michaelson, M. Dror Negrier, Sylvie Kim, Sindy T. Huang, Xin Williams, J. Andrew Eisen, Tim Motzer, Robert J. TI Circulating proteins as potential biomarkers of sunitinib and interferon-alpha efficacy in treatment-na < ve patients with metastatic renal cell carcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Metastatic renal cell carcinoma; Sunitinib; Biomarkers; Phase III clinical trial ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III TRIAL; TYROSINE KINASE INHIBITOR; IN-VIVO; 1ST-LINE SUNITINIB; ANTITUMOR-ACTIVITY; FACTOR RECEPTORS; UP-REGULATION; DOUBLE-BLIND; ANGIOGENESIS AB We investigated potential biomarkers of efficacy in a phase III trial of sunitinib versus interferon-alpha (IFN-alpha), first-line in metastatic renal cell carcinoma (mRCC), by analyzing plasma levels of vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGF receptor-3 (sVEGFR-3) and interleukin (IL)-8. Seven hundred and fifty mRCC patients were randomized to oral sunitinib 50 mg/day in repeated cycles of a 4-week on/2-week off schedule or IFN-alpha 9 million units subcutaneously thrice weekly. Plasma samples collected from a subset of 63 patients on days 1 and 28 of cycles 1-4 and at end of treatment were analyzed by ELISA. Baseline characteristics of biomarker-evaluated patients in sunitinib (N = 33) and IFN-alpha (N = 30) arms were comparable to their respective intent-to-treat populations. By univariate Cox regression analysis, low baseline soluble protein levels were associated with lower risk of progression/death (all P < 0.05): in both treatment arms, baseline VEGF-A and IL-8 were associated with overall survival (OS) and baseline VEGF-C with progression-free survival (PFS); in the sunitinib arm, baseline VEGF-A was associated with PFS and baseline sVEGFR-3 with PFS and OS; in the IFN-alpha arm, baseline IL-8 was associated with PFS. In multivariate analysis, baseline sVEGFR-3 and IL-8 remained independent predictors of OS in the sunitinib arm, while no independent predictors of outcome remained in the IFN-alpha arm. Pharmacodynamic changes were not associated with PFS or OS for any plasma protein investigated. Our findings suggest that, in mRCC, baseline VEGF-A and IL-8 may have prognostic value, while baseline sVEGFR-3 may predict sunitinib efficacy. C1 [Harmon, Charles S.; DePrimo, Samuel E.; Kim, Sindy T.; Huang, Xin; Williams, J. Andrew] Pfizer Oncol, San Diego, CA 92121 USA. [Figlin, Robert A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Hudes, Gary R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Hutson, Thomas E.] Baylor Sammons Canc Ctr Texas Oncol PA, Dallas, TX USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Negrier, Sylvie] Ctr Leon Berard, F-69373 Lyon, France. [Eisen, Tim] Cambridge Univ Hlth Partners, Addenbrookes Hosp, Cambridge, England. [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Williams, JA (reprint author), Pfizer Oncol, 10646 Sci Ctr Dr, San Diego, CA 92121 USA. EM james.williams2@pfizer.com FU Pfizer Inc. FX We thank all of the participating patients and their families, as well as the investigators, research nurses, study coordinators and operations staff. The study was sponsored by Pfizer Inc. Charles Harmon was an employee of Atrium Staffing (New York, NY, USA) and was a paid contractor of Pfizer in the development of this manuscript and the analysis and interpretation of the data. Editorial/medical writing support was provided by Jean Scott and Felicity Leigh at ACUMED (R) (Tytherington, UK) and was funded by Pfizer Inc. NR 49 TC 22 Z9 23 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2014 VL 73 IS 1 BP 151 EP 161 DI 10.1007/s00280-013-2333-4 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 283CU UT WOS:000329223200018 PM 24220935 ER PT J AU Owonikoko, TK Aisner, J Wang, XV Dahlberg, SE Rubin, EH Ramalingam, SS Gounder, M Rausch, PG Axelrod, RS Schiller, JH AF Owonikoko, Taofeek K. Aisner, Joseph Wang, Xin Victoria Dahlberg, Suzanne E. Rubin, Eric H. Ramalingam, Suresh S. Gounder, Murugesan Rausch, Paul Gregory Axelrod, Rita S. Schiller, Joan H. TI E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Small cell; Topoisomerase; Clinical trial; Topotecan; Irinotecan; Sequential administration; Survival ID COOPERATIVE-ONCOLOGY-GROUP; 1ST-LINE TREATMENT; TOPOISOMERASE-I; PLUS CISPLATIN; ORAL ETOPOSIDE; TRIAL; CHEMOTHERAPY; DISEASE; CAMPTOTHECIN; CARBOPLATIN AB Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC). Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO bid) on days 3 and 10 (PIE) in a 3-week cycle. We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade a parts per thousand yen3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1-78.9, 95 % CI 57.1-80.4 %) for arm A and 57.6 % (90 % CI 46.7-67.9, 95 % CI 44.8-69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4-7.5 months) and 11.9 months (95 % CI 9.6-13.7 months) for arm A and 6.0 months (95 % CI 5.4-7.0 months) and 11.0 months (95 % CI 8.6-13.1 months) for arm B. Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC. C1 [Owonikoko, Taofeek K.; Ramalingam, Suresh S.] Emory Univ, Atlanta, GA 30322 USA. [Aisner, Joseph; Gounder, Murugesan] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Wang, Xin Victoria; Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wang, Xin Victoria; Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Rubin, Eric H.] Merck Res Labs, N Wales, PA USA. [Rausch, Paul Gregory] Frederick Mem Hosp, Frederick, MA USA. [Axelrod, Rita S.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Aisner, J (reprint author), Rutgers Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08901 USA. EM aisnerjo@cinj.rutgers.edu FU Public Health Service [CA23318, CA66636, CA21115, CA107868, CA16116, CA13650]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA107868, CA16116, CA13650 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 43 TC 2 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2014 VL 73 IS 1 BP 171 EP 180 DI 10.1007/s00280-013-2338-z PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 283CU UT WOS:000329223200020 PM 24288121 ER PT J AU Molina, AM Hutson, TE Larkin, J Gold, AM Wood, K Carter, D Motzer, R Michaelson, MD AF Molina, Ana M. Hutson, Thomas E. Larkin, James Gold, Anne M. Wood, Karen Carter, Dave Motzer, Robert Michaelson, M. Dror TI A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Lenvatinib; Everolimus; Metastatic renal cell carcinoma; Antitumor; mTOR; VEGF ID TARGETED THERAPIES; SOLID TUMORS; CANCER; BEVACIZUMAB; SORAFENIB; SUNITINIB; OPPORTUNITIES; MTOR AB Lenvatinib is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFR beta, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). This phase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. Patients with advanced unresectable or mRCC and Eastern Cooperative Oncology Group performance status 0-1 were eligible (number of prior treatments not restricted). Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28-day cycles using a conventional 3 + 3 dose-escalation design. At the MTD, additional patients were enrolled in an expansion cohort. Twenty patients (mean 58.4 years) received lenvatinib [12 mg (n = 7); 18 mg (n = 11); 24 mg (n = 2)] plus everolimus 5 mg. MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg. The most common treatment-related treatment-emergent adverse events (all dosing cohorts) were fatigue 60 % (Grade a parts per thousand yen3: 10 %), mucosal inflammation 50 %, proteinuria (Grade a parts per thousand yen3: 15 %), diarrhea (Grade a parts per thousand yen3: 10 %), vomiting (Grade a parts per thousand yen3: 5 %), hypertension, and nausea, each 40 %. In MTD and lowest-dose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. C1 [Molina, Ana M.; Motzer, Robert] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Hutson, Thomas E.] Texas Oncol, Dallas, TX USA. [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England. [Gold, Anne M.] Eisai Inc, Woodcliff Lake, NJ USA. [Wood, Karen; Carter, Dave] Eisai Ltd, Hatfield, Herts, England. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Molina, AM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM molinaa@mskcc.org OI Michaelson, Dror/0000-0001-9249-6338 FU Eisai Inc. FX This work was supported by Eisai Inc. The authors would like to thank Phase Five Communications Inc. for medical editorial assistance with this manuscript and C. Andresen, former employee of Eisai Inc., for medical monitoring. We also thank the commitment of participating patients, their families, and the study investigators for their invaluable contribution to this research. NR 34 TC 24 Z9 26 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2014 VL 73 IS 1 BP 181 EP 189 DI 10.1007/s00280-013-2339-y PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 283CU UT WOS:000329223200021 PM 24190702 ER PT J AU Itani, KMF Shorr, AF AF Itani, Kamal M. F. Shorr, Andrew F. TI FDA Guidance for ABSSSI Trials: Implications for Conducting and Interpreting Clinical Trials SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SKIN-STRUCTURE INFECTIONS; ACUTE BACTERIAL SKIN; VANCOMYCIN PLUS AZTREONAM; SOFT-TISSUE INFECTIONS; COMPLICATED SKIN; CONTROLLED SERIES; END-POINTS; 2-PHASE 3; CANVAS 1; CEFTAROLINE AB Recent guidance from the US Food and Drug Administration (FDA) on the conduct of clinical trials for acute bacterial skin and skin structure infection (ABSSSI) has changed the framework for clinical trial design and conduct. Notable changes included new disease state definitions, new primary endpoint definitions and the timing of assessments at these endpoints, and updated guidance on patient inclusion/exclusion criteria. Supportive evidence and statistical justification for the proposed noninferiority margins were described in detail. Although the updated guidelines are still considered drafts and have been adopted in some trials, they serve as the basis for study protocol discussions between pharmaceutical companies and the FDA in advancing the development of promising new agents. Not only will the new trial designs impact researchers and sponsors responsible for drug development programs, but they will also affect healthcare providers participating in clinical trials and the ways in which clinicians develop patient treatment plans based on the results of those trials. This review provides a summary of key changes that will impact future clinical trial design and outcomes. C1 [Itani, Kamal M. F.] Boston Univ, VA Boston Healthcare Syst, Dept Surg, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Shorr, Andrew F.] Washington Hosp Ctr, Dept Pulm & Crit Care, Washington, DC 20010 USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, West Roxbury Campus,1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM kitani@va.gov FU Cubist Pharmaceuticals FX Technical and editorial assistance with this manuscript was provided by Bill Jacobs, PhD (Strategic HealthCOM, Somerville, NJ), funded by Cubist Pharmaceuticals, and by Dominik Wolf, an employee of Cubist Pharmaceuticals. NR 23 TC 16 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2014 VL 58 SU 1 BP S4 EP S9 DI 10.1093/cid/cit612 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 280QH UT WOS:000329045300002 PM 24343831 ER PT J AU Sullivan, DR Ganzini, L Duckart, JP Lopez-Chavez, A Deffebach, ME Thielke, SM Slatore, CG AF Sullivan, D. R. Ganzini, L. Duckart, J. P. Lopez-Chavez, A. Deffebach, M. E. Thielke, S. M. Slatore, C. G. TI Treatment Receipt and Outcomes among Lung Cancer Patients with Depression SO CLINICAL ONCOLOGY LA English DT Article DE Depression; epidemiology; lung cancer; lung cancer treatment; patient outcomes ID EARLY PALLIATIVE CARE; QUALITY-OF-LIFE; SMALL-CELL; SMOKING-CESSATION; PROGNOSTIC VALUE; OLDER-ADULTS; SURVIVAL; COMORBIDITY; PREDICTORS; CHEMOTHERAPY AB Aims: Among lung cancer patients, depression has been associated with increased mortality, although the mechanisms are unknown. We evaluated the association of depression with mortality and receipt of cancer therapies among depressed veterans with lung cancer. Materials and methods: A retrospective, cohort study of lung cancer patients in the Veterans Affairs-Northwest Health Network from 1995 to 2010. Depression was defined by ICD-9 coding within 24 months before lung cancer diagnosis. Multivariable Cox proportional analysis and logistic regression were used. Results: In total, 3869 lung cancer patients were evaluated; 14% had a diagnosis of depression. A diagnosis of depressionwas associated with increased mortality among all stage lung cancer patients (hazard ratio 1.14, 95% confidence interval: 1.03-1.27, P = 0.01). Among early-stage (I and II) non-small cell lung cancer (NSCLC) patients, the hazard ratio was 1.37 (95% confidence interval: 1.12-1.68, P = 0.003). There was no association of depression diagnosis with surgery (odds ratio 0.83, 95% confidence interval: 0.56-1.22, P = 0.34) among early-stage NSCLC patients. A depression diagnosis was not associated with mortality (hazard ratio 1.02, 95% confidence interval: 0.89-1.16, P = 0.78) or chemotherapy (odds ratio 1.07, 95% confidence interval: 0.83-1.39, P = 0.59) or radiation (odds ratio 1.04, 95% confidence interval: 0.81-1.34, P = 0.75) receipt among advanced-stage (III and IV) NSCLC patients. Increased utilisation of health services for depression was associated with increased mortality among depressed patients. Conclusions: Depression is associated with increased mortality in lung cancer patients and this association is higher among those with increased measures of depression care utilisation. Differences in lung cancer treatment receipt are probably not responsible for the observed mortality differences between depressed and non-depressed patients. Clinicians should recognise the significant effect of depression on lung cancer survival. (c) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Sullivan, D. R.; Ganzini, L.; Duckart, J. P.; Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Sullivan, D. R.; Deffebach, M. E.; Slatore, C. G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Lopez-Chavez, A.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Deffebach, M. E.; Slatore, C. G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Thielke, S. M.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Thielke, S. M.] Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA. [Thielke, S. M.] Puget Sound Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Sullivan, DR (reprint author), 3710 SW US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM sullivad@ohsu.edu OI Sullivan, Donald/0000-0003-3266-3389; Slatore, Christopher/0000-0003-0958-8122 FU NIH [5 T32 HL083808-05-32]; VA HSR&D Career Development Award; NIMH Beeson Career Development Award [K23MH093591]; Portland Veterans Affairs Medical Center, Portland, Oregon; Veterans Affairs Puget Sound Healthcare System, Seattle, Washington FX Dr Sullivan takes responsibility for the content of the manuscript, including the data and analysis. All authors have participated sufficiently in the conception and design of this work or the analysis and interpretation of the data, as well as the writing of the manuscript, to take public responsibility for it. All authors believe the manuscript represents valid work. All authors have reviewed the final version, and approve it for publication. Dr Sullivan is supported by a NIH T-32 (5 T32 HL083808-05-32). Dr Slatore is supported by a VA HSR&D Career Development Award. Dr Thielke is supported by an NIMH Beeson Career Development Award (K23MH093591). This study is the result of work supported by resources from the Portland Veterans Affairs Medical Center, Portland, Oregon and the Veterans Affairs Puget Sound Healthcare System, Seattle, Washington. The Department of Veterans Affairs did not have a role in the conduct of the study, in the collection, management, analysis or interpretation of data, or in the preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 46 TC 5 Z9 5 U1 4 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 EI 1433-2981 J9 CLIN ONCOL-UK JI Clin. Oncol. PD JAN PY 2014 VL 26 IS 1 BP 25 EP 31 DI 10.1016/j.clon.2013.09.001 PG 7 WC Oncology SC Oncology GA 281RJ UT WOS:000329118400005 PM 24080122 ER PT J AU Bozic, KJ Lau, E Ong, K Chan, V Kurtz, S Vail, TP Rubash, HE Berry, DJ AF Bozic, Kevin J. Lau, Edmund Ong, Kevin Chan, Vanessa Kurtz, Steven Vail, Thomas P. Rubash, Harry E. Berry, Daniel J. TI Risk Factors for Early Revision After Primary TKA in Medicare Patients SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Open Scientific Meeting of The-Knee-Society CY MAR 23, 2013 CL Chicago, IL ID TOTAL KNEE ARTHROPLASTY; PERIPROSTHETIC JOINT INFECTION; TOTAL HIP; REPLACEMENT; COMORBIDITY; RATES AB Patient, surgeon, health system, and device factors are all known to influence outcomes in total knee arthroplasty (TKA). However, patient-related factors associated with an increased risk of early failure are not well understood, particularly in elderly patients. The purpose of this study was to identify specific comorbid conditions associated with increased risk of early revision in Medicare patients undergoing TKA. A total of 117,903 Medicare patients who underwent primary TKA between 1998 and 2010 were identified from the Medicare 5% national sample administrative database and used to determine the relative risk of revision within 12 months after primary TKA as a function of baseline medical comorbidities. Cox regression was used to evaluate the impact of 29 comorbid conditions on risk of early failure controlling for age, sex, race, census region, socioeconomic status, and all other baseline comorbidities. The most significant independent risk factors for revision TKA within 12 months were chronic pulmonary disease, depression, alcohol abuse, drug abuse, renal disease, hemiplegia or paraplegia, and obesity. This information could be valuable to patients and their surgeons when making shared medical decisions regarding elective TKA and for risk-stratifying publicly reported outcomes in Medicare patients undergoing TKA. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Bozic, Kevin J.; Chan, Vanessa; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.; Chan, Vanessa] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Lau, Edmund] Exponent Inc, Menlo Pk, CA USA. [Ong, Kevin; Kurtz, Steven] Exponent Inc, Philadelphia, PA USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus MU 320W, San Francisco, CA 94143 USA. EM kevin.bozic@ucsf.edu FU Orthopaedic Research and Education Foundation (Rosemont, IL, USA); Exponent, Inc (Philadelphia, PA, USA); Exponent, Inc.; DePuy Orthopaedics, Inc (Warsaw, IN, USA); DePuy Orthopaedics, Inc.; Zimmer, Inc (Warsaw, IN, USA) FX The institution of one or more of the authors (KJB) has received, during the study period, funding from the Orthopaedic Research and Education Foundation (Rosemont, IL, USA). One of the authors (SMK) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, an amount in excess of USD 100,000, from Exponent, Inc (Philadelphia, PA, USA). One of the authors (KO) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, an amount in excess of USD 100,000, from Exponent, Inc. One of the authors (EL) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, an amount in excess of USD 100,000, from Exponent, Inc. One of the authors (DJB) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, an amount in excess of USD 100,000, from DePuy Orthopaedics, Inc (Warsaw, IN, USA). One of the authors (TPV) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, an amount in excess of USD 10,000, from DePuy Orthopaedics, Inc. One of the authors (HER) certifies that he, or a member of his immediate family, has received or may receive payments or benefits, during the study period, an amount in excess of USD 100,000, from Zimmer, Inc (Warsaw, IN, USA). NR 21 TC 29 Z9 29 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2014 VL 472 IS 1 BP 232 EP 237 DI 10.1007/s11999-013-3045-0 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 277MT UT WOS:000328824400036 PM 23661301 ER PT J AU Solomon, B Wilner, KD Shaw, AT AF Solomon, B. Wilner, K. D. Shaw, A. T. TI Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ALK GENE REARRANGEMENT; RECEPTOR TYROSINE KINASE; EML4-ALK FUSION GENE; WILD-TYPE EGFR; CRIZOTINIB RESISTANCE; ACTIVATING MUTATIONS; ONCOGENIC MUTATIONS; CLINICAL-FEATURES; MET AMPLIFICATION; NEVER-SMOKERS AB The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in similar to 3-5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. Single-arm studies demonstrating rapid and durable responses in the majority of ALK-positive NSCLC patients treated with crizotinib have been followed by a randomized phase Ill clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802802), and AP26113, and heat shock protein 90 inhibitors. C1 [Solomon, B.] Peter MacCallum Canc Ctr, Dept Med Oncol, East Melbourne, Vic, Australia. [Solomon, B.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia. [Wilner, K. D.] Pfizer, La Jolla, CA USA. [Shaw, A. T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. EM ashaw1@partners.org NR 96 TC 33 Z9 36 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2014 VL 95 IS 1 BP 15 EP 23 DI 10.1038/clpt.2013.200 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 278VX UT WOS:000328919100010 PM 24091716 ER PT J AU Boucher, J Kleinridders, A Kahn, CR AF Boucher, Jeremie Kleinridders, Andre Kahn, C. Ronald TI Insulin Receptor Signaling in Normal and Insulin-Resistant States SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; ENDOPLASMIC-RETICULUM STRESS; NECROSIS-FACTOR-ALPHA; DIET-INDUCED OBESITY; MOUSE SKELETAL-MUSCLE; PHOSPHATIDYLINOSITOL 3-KINASE P85-ALPHA; SUBSTRATE-1 TYROSINE PHOSPHORYLATION; STIMULATED GLUCOSE-TRANSPORT; REGULATORY SUBUNIT P85-ALPHA; GLYCOGEN-SYNTHASE KINASE-3 AB In the wake of the worldwide increase in type-2 diabetes, a major focus of research is understanding the signaling pathways impacting this disease. Insulin signaling regulates glucose, lipid, and energy homeostasis, predominantly via action on liver, skeletal muscle, and adipose tissue. Precise modulation of this pathway is vital for adaption as the individual moves from the fed to the fasted state. The positive and negative modulators acting on different steps of the signaling pathway, as well as the diversity of protein isoform interaction, ensure a proper and coordinated biological response to insulin in different tissues. Whereas genetic mutations are causes of rare and severe insulin resistance, obesity can lead to insulin resistance through a variety of mechanisms. Understanding these pathways is essential for development of new drugs to treat diabetes, metabolic syndrome, and their complications. C1 [Boucher, Jeremie; Kleinridders, Andre; Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Boucher, Jeremie; Kleinridders, Andre; Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Boucher, Jeremie; Kleinridders, Andre; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, 75 Francis St, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu NR 246 TC 38 Z9 38 U1 6 U2 26 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JAN PY 2014 VL 6 IS 1 AR a009191 DI 10.1101/cshperspect.a009191 PG 23 WC Cell Biology SC Cell Biology GA 282ZO UT WOS:000329214100002 ER PT J AU Thobakgale, CF Ndung'u, T AF Thobakgale, Christina F. Ndung'u, Thumbi TI Neutrophil counts in persons of African origin SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE Africans; antimicrobial immunity; Duffy-null; neutrophils; phenotype ID DUFFY ANTIGEN RECEPTOR; BLOOD-CELL COUNT; POLYMORPHONUCLEAR NEUTROPHILS; PRIMARY IMMUNODEFICIENCY; PLASMODIUM-FALCIPARUM; DISEASE PROGRESSION; HIV-1 ACQUISITION; CHEMOKINES; EXPRESSION; INFECTION AB Purpose of reviewThe causes of ethnic or benign neutropenia have long been unclear. Here, we discuss the emerging data on the causes and consequences of neutropenia and discuss the relevance of these data for African populations, in which the prevalence of neutropenia is high.Recent findingsGenetic deletion of the Duffy antigen receptor for chemokines (DARC-null genotype) has been identified as a major determinant for neutropenia. DARC acts as a receptor for Plasmodium vivax malaria and the DARC-null genotype has thus been positively selected among Africans; however, recent studies suggest that Duffy-null-linked neutropenia could increase the risk of HIV infection. Data are emerging that neutrophils are versatile cells that play a critical role not only in direct antimicrobial activity but also in priming and regulating the activity of other innate and adaptive immune cells. Therefore, we discuss here the imperative to better understand the causes, consequences, and the underlying mechanisms of neutropenia among Africans as a prerequisite for rational and optimal biomedical interventions to improve health outcomes.SummaryNeutropenia among Africans, linked to the Duffy-null trait or otherwise, may have significant health consequences that remain largely undetermined and could have a significant impact on the pathogenesis of diseases. C1 [Thobakgale, Christina F.; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Thobakgale, Christina F.; Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Thobakgale, Christina F.; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Thobakgale, Christina F.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, 719 Umbilo Rd, ZA-4013 Durban, South Africa. EM ndungu@ukzn.ac.za OI Ndung'u, Thumbi/0000-0003-2962-3992 FU South African Research Chairs Initiative of the South African Department of Science and Technology through the National Research Foundation; International AIDS Vaccine Initiative; Victor Daitz Chair in HIV/TB Research; International Early Career Scientist Award from the Howard Hughes Medical Institute FX The authors would like to thank Kewreshini Naidoo for assistance with literature scans and Siyabonga Nikwe for assistance with graphic illustrations. Research work in the authors' laboratory is funded by the South African Research Chairs Initiative of the South African Department of Science and Technology through the National Research Foundation. Additional funding was received from the International AIDS Vaccine Initiative, the Victor Daitz Chair in HIV/TB Research, and an International Early Career Scientist Award from the Howard Hughes Medical Institute. NR 58 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2014 VL 21 IS 1 BP 50 EP 57 DI 10.1097/MOH.0000000000000007 PG 8 WC Hematology SC Hematology GA 282PT UT WOS:000329185200010 PM 24257098 ER PT J AU Stossel, TP Dale, DC AF Stossel, Thomas P. Dale, David C. TI Editorial introductions SO CURRENT OPINION IN HEMATOLOGY LA English DT Editorial Material C1 [Stossel, Thomas P.; Dale, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stossel, Thomas P.] Boston Childrens Hosp, Boston, MA USA. [Stossel, Thomas P.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Stossel, Thomas P.] Harvard Univ, Med School, Cambridge, MA 02138 USA. [Dale, David C.] Univ Washington, Seattle, WA 98195 USA. [Dale, David C.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Dale, David C.] NIAID, NIH, Bethesda, MD USA. RP Stossel, TP (reprint author), Massachusetts Gen Hosp, Div Translat Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2014 VL 21 IS 1 DI 10.1097/MOH.0000000000000013 PG 2 WC Hematology SC Hematology GA 282PT UT WOS:000329185200001 ER PT J AU Troughton, R Felker, GM Januzzi, JL AF Troughton, Richard Felker, G. Michael Januzzi, James L., Jr. TI Natriuretic peptide-guided heart failure management SO EUROPEAN HEART JOURNAL LA English DT Review DE Heart failure; Natriuretic peptides; Management; Outcomes ID STANDARD MEDICAL THERAPY; CARDIAC RESYNCHRONIZATION THERAPY; VENTRICULAR SYSTOLIC DYSFUNCTION; ROSUVASTATIN MULTINATIONAL TRIAL; EJECTION FRACTION FINDINGS; NT-PROBNP; ELDERLY-PATIENTS; RANDOMIZED-TRIAL; TIME-CHF; MULTIDISCIPLINARY CARE AB The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B-type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT-proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BNP and NT-proBNP relative to therapeutic intervention in HF has led to the concept of using the biomarkers as a guide for intensification of HF care with a goal of not only achieving guideline-directed medical therapy goals accompanied by targeted natriuretic peptide suppression below prognostic thresholds. In studies achieving this combination of therapy optimization and BNP/NT-proBNP suppression, superior outcomes have been observed, and the approach was well tolerated. Natriuretic peptide-guided HF therapy has recently been given a recommendation in US HF guidelines to achieve guideline-directed medical therapy (Class IIa) and possibly improve outcome (Class IIb), while other clinical practice guidelines (including those from the European Society of Cardiology) await results from emerging clinical trial data. We will review lessons learned in the past regarding this novel concept of biomarker guided HF care, and discuss future directions for the approach. C1 [Troughton, Richard] Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand. [Felker, G. Michael] Duke Univ, Med Ctr, Durham, NC USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU NHLBI; Roche Diagnostics; Amgen; Otsuka; Critical Diagnostics; BG Medicine; Thermo Fisher; Siemens AG FX R.T. has received honoraria from Roche Diagnostics and consultant income from St Jude Medical. G. M. F has received grant support from NHLBI, Roche Diagnostics, Amgen, and Otsuka, and acted as a consultant for Amgen, Novartis, Roche Diagnostics, Medtronic, Merck, Singulex, BG Medicine, Trevena, Celladon, St Judes, and Zensun. J.L.J. has received grant support from Roche Diagnostics, Critical Diagnostics, BG Medicine, Thermo Fisher, and Siemens AG. NR 62 TC 46 Z9 48 U1 5 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2014 VL 35 IS 1 BP 16 EP + DI 10.1093/eurheartj/eht463 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 283ME UT WOS:000329249400009 PM 24216390 ER PT J AU VanDussen, KL Liu, TC Li, DL Towfic, F Modiano, N Winter, R Haritunians, T Taylor, KD Dhall, D Targan, SR Xavier, RJ McGovern, DPB Stappenbeck, TS AF VanDussen, Kelli L. Liu, Ta-Chiang Li, Dalin Towfic, Fadi Modiano, Nir Winter, Rachel Haritunians, Talin Taylor, Kent D. Dhall, Deepti Targan, Stephan R. Xavier, Ramnik J. McGovern, Dermot P. B. Stappenbeck, Thaddeus S. TI Genetic Variants Synthesize to Produce Paneth Cell Phenotypes That Define Subtypes of Crohn's Disease SO GASTROENTEROLOGY LA English DT Article DE Pathogenesis; Prognostic Factor; Diagnosis; Inflammatory Bowel Disease ID INFLAMMATORY-BOWEL-DISEASE; EPITHELIOID GRANULOMAS; NOD2/CARD15 MUTATIONS; NOD2; SUSCEPTIBILITY; EXPRESSION; AUTOPHAGY; ATG16L1; PATHOGENESIS; RECOGNITION AB BACKGROUND & AIMS: Genetic susceptibility loci for Crohn's disease (CD) are numerous, complex, and likely interact with undefined components of the environment. It has been a challenge to link the effects of particular loci to phenotypes of cells associated with pathogenesis of CD, such as Paneth cells. We investigated whether specific phenotypes of Paneth cells associated with particular genetic susceptibility loci can be used to define specific subtypes of CD. METHODS: We performed a retrospective analysis of 119 resection specimens collected from patients with CD at 2 separate medical centers. Paneth cell phenotypes were classified as normal or abnormal (with disordered, diminished, diffuse, or excluded granule phenotypes) based on lysozyme-positive secretory granule morphology. To uncover the molecular basis of the Paneth cell phenotypes, we developed methods to determine transcriptional profiles from whole-thickness and laser-capture microdissected, formalin-fixed, paraffin-embedded tissue sections. RESULTS: The proportion of abnormal Paneth cells was associated with the number of CD-associated NOD2 risk alleles. The cumulative number of NOD2 and ATG16L1 risk alleles had an additive effect on the proportion of abnormal Paneth cells. Unsupervised clustering analysis of demographic and Paneth cell data divided patients into 2 principal subgroups, defined by high and low proportions of abnormal Paneth cells. The disordered and diffuse abnormal Paneth cell phenotypes were associated with an altered transcriptional signature of immune system activation. We observed an inverse correlation between abnormal Paneth cells and presence of granuloma. In addition, high proportions of abnormal Paneth cells were associated with shorter time to disease recurrence after surgery. CONCLUSIONS: Histologic analysis of Paneth cell phenotypes can be used to divide patients with CD into subgroups with distinct pathognomonic and clinical features. C1 [VanDussen, Kelli L.; Liu, Ta-Chiang; Stappenbeck, Thaddeus S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Li, Dalin; Modiano, Nir; Winter, Rachel; Haritunians, Talin; Targan, Stephan R.; McGovern, Dermot P. B.] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA. [Li, Dalin; Haritunians, Talin; Taylor, Kent D.; McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Dhall, Deepti] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. [Towfic, Fadi; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Towfic, Fadi; Xavier, Ramnik J.] Broad Inst, Boston, MA USA. RP Stappenbeck, TS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Box 8118, St Louis, MO 63110 USA. EM Dermot.McGovern@cshs.org; stappenb@pathology.wustl.edu OI VanDussen, Kelli/0000-0002-5810-0720 FU National Institutes of Health [T32 AI007163]; Washington University Institute of Clinical and Translational Sciences [CTSA308]; National Institute of Diabetes and Digestive and Kidney Disease [P30DK052574]; US Public Health Service [PO1DK046763]; Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute; National Center for Research Resources [M01-RR00425]; UCLA/Cedars-Sinai/Harbor/Drew Clinical and Translational Science Institute [UL1 TR000124-01]; Southern California Diabetes and Endocrinology Research grant [DK063491]; Helmsley Charitable Trust; European Union; Crohn's and Colitis Foundation of America (CCFA); Feintech Family Chair in IBD; Joshua L. and Lisa Z. Greer Chair in IBD Genetics; CCFA Genetics initiative; [DK043351]; [DK097485]; [DK092405]; [DK062413]; [DK046763-19]; [AI067068]; [HS021747]; [AI084887] FX K.L.V. was supported by a National Institutes of Health training grant (T32 AI007163). The research was funded by a Washington University Institute of Clinical and Translational Sciences Pilot Award (CTSA308). The Washington University Digestive Disease Research Core Center is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Disease (P30DK052574). IBD Research at Cedars-Sinai is supported by US Public Health Service grant PO1DK046763 and the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Research Funds. Genotyping at Cedars-Sinai Medical Center is supported in part by the National Center for Research Resources grant M01-RR00425, UCLA/Cedars-Sinai/Harbor/Drew Clinical and Translational Science Institute grant (UL1 TR000124-01), the Southern California Diabetes and Endocrinology Research grant (DK063491). Project investigators are supported by The Helmsley Charitable Trust (D.P.B.M.), The European Union (D.P.B.M.), The Crohn's and Colitis Foundation of America (CCFA) (D.P.B.M.), The Feintech Family Chair in IBD (S.R.T.), The Joshua L. and Lisa Z. Greer Chair in IBD Genetics (D.P.B.M.), and grants DK043351, DK097485, DK092405 (R.J.X.), DK062413, DK046763-19, AI067068, HS021747 (D.P.B.M.), and AI084887 (T.S.S.). T.S.S. and R.J.X. are supported by the CCFA Genetics initiative. NR 43 TC 35 Z9 35 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2014 VL 146 IS 1 BP 200 EP 209 DI 10.1053/j.gastro.2013.09.048 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 276GF UT WOS:000328736000034 PM 24076061 ER PT J AU Bailey, JM Alsina, J Rasheed, ZA McAllister, FM Fu, YY Plentz, R Zhang, H Pasricha, PJ Bardeesy, N Matsui, W Maitra, A Leach, SD AF Bailey, Jennifer M. Alsina, Janivette Rasheed, Zeshaan A. McAllister, Florencia M. Fu, Ya-Yuan Plentz, Ruben Zhang, Hao Pasricha, Pankaj J. Bardeesy, Nabeel Matsui, William Maitra, Anirban Leach, Steven D. TI DCLK1 Marks a Morphologically Distinct Subpopulation of Cells With Stem Cell Properties in Preinvasive Pancreatic Cancer SO GASTROENTEROLOGY LA English DT Article DE PanIN; Kras; Notch; Acetylated Tubulin ID INTRAEPITHELIAL NEOPLASIA; TUMOR-GROWTH; CAM KINASE-LIKE-1; ALPHA-TUBULIN; ADENOCARCINOMA; IDENTIFICATION; MOUSE; DOUBLECORTIN; MICE; ACETYLTRANSFERASE AB BACKGROUND & AIMS: As in other tumor types, progression of pancreatic cancer may require a functionally unique population of cancer stem cells. Although such cells have been identified in many invasive cancers, it is not clear whether they emerge during early or late stages of tumorigenesis. Using mouse models and human pancreatic cancer cell lines, we investigated whether preinvasive pancreatic neoplasia contains a subpopulation of cells with distinct morphologies and cancer stem cell-like properties. METHODS: Pancreatic tissue samples were collected from the KCPdx1, KPCPdx1, and KCiMist1 mouse models of pancreatic intraepithelial neoplasia (PanIN) and analyzed by confocal and electron microscopy, lineage tracing, and fluorescence-activated cell sorting. Subpopulations of human pancreatic ductal adenocarcinoma (PDAC) cells were similarly analyzed and also used in complementary DNA microarray analyses. RESULTS: The microtubule regulator DCLK1 marked a morphologically distinct and functionally unique population of pancreatic cancer-initiating cells. These cells displayed morphological and molecular features of gastrointestinal tuft cells. Cells that expressed DCLK1 also expressed high levels of ATAT1, HES1, HEY1, IGF1R, and ABL1, and manipulation of these pathways in PDAC cell lines inhibited their clonogenic potential. Pharmacological inhibition of g-secretase activity reduced the abundance of these cells in murine PanIN in a manner that correlated with inhibition of PanIN progression. CONCLUSIONS: Human PDAC cells and pancreatic neoplasms in mice contain morphologically and functionally distinct subpopulations that have cancer stem cell-like properties. These populations can be identified at the earliest stages of pancreatic tumorigenesis and provide new cellular and molecular targets for pancreatic cancer treatment and/or chemoprevention. C1 [Bailey, Jennifer M.; Alsina, Janivette; Leach, Steven D.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Bailey, Jennifer M.; Leach, Steven D.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Rasheed, Zeshaan A.; McAllister, Florencia M.; Matsui, William] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Fu, Ya-Yuan; Pasricha, Pankaj J.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Maitra, Anirban] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Plentz, Ruben; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Med, Boston, MA 02114 USA. [Plentz, Ruben] Med Univ Hosp, Dept Internal Med, Tubingen, Germany. [Zhang, Hao] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Leach, SD (reprint author), 733 N Broadway,MRB 471, Baltimore, MD 21205 USA. EM stleach@jhmi.edu OI Matsui, William/0000-0002-3088-0964; Fu, Ya-Yuan/0000-0002-3894-0490 FU Pancreatic Cancer Action Network-AACR Pathway to Leadership Award; National Cancer Institute [5F32 CA157044, P01 CA134292]; immixGroup Foundation; National Institute of General Medical Sciences [T32GMO66691]; Pancreatic Cancer Action Network-AACR Fellowship [12-40-25-MCAL]; Conquer Cancer Foundation; Sol Goldman Pancreatic Cancer Research Center; Johns Hopkins University; [5T32 CA126607]; [R01 CA150142] FX J.M.B. was supported by the 2011 Pancreatic Cancer Action Network-AACR Pathway to Leadership Award and National Cancer Institute grant 5F32 CA157044. J.A. was supported through 5T32 CA126607 and the immixGroup Foundation Fellowship. Z.A.R. was supported by the Pancreatic Cancer Action Network-AACR Pathway to Leadership Award. F.M.M. was supported by National Institute of General Medical Sciences grant T32GMO66691, the 2012 Pancreatic Cancer Action Network-AACR Fellowship, in memory of Samuel Stroum, grant 12-40-25-MCAL, and the 2012 Conquer Cancer Foundation Young Investigator Award. W.M. was supported by grant R01 CA150142. S.D.L. and A.M. were supported by National Cancer Institute grant P01 CA134292. S.D.L. was further supported by a funding from the Sol Goldman Pancreatic Cancer Research Center and by the Paul K. Neumann Professorship in Pancreatic Cancer at Johns Hopkins University. NR 38 TC 52 Z9 54 U1 0 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2014 VL 146 IS 1 BP 245 EP 256 DI 10.1053/j.gastro.2013.09.050 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 276GF UT WOS:000328736000038 PM 24096005 ER PT J AU Al-Hawary, MM Francis, IR Chari, ST Fishman, EK Hough, DM Lu, DS Macari, M Megibow, AJ Miller, FH Mortele, KJ Merchant, NB Minter, RM Tamm, EP Sahani, DV Simeone, DM AF Al-Hawary, Mahmoud M. Francis, Isaac R. Chari, Suresh T. Fishman, Elliot K. Hough, David M. Lu, David S. Macari, Michael Megibow, Alec J. Miller, Frank H. Mortele, Koenraad J. Merchant, Nipun B. Minter, Rebecca M. Tamm, Eric P. Sahani, Dushyant V. Simeone, Diane M. TI Pancreatic Ductal Adenocarcinoma Radiology Reporting Template: Consensus Statement of the Society of Abdominal Radiology and the American Pancreatic Association SO GASTROENTEROLOGY LA English DT Article ID DETERMINING RESECTABILITY; PREOPERATIVE THERAPY; MULTIDETECTOR CT; SECONDARY SIGNS; CANCER; MDCT; PANCREATICODUODENECTOMY; DIAGNOSIS; SURVIVAL; UPDATE AB Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions. C1 [Al-Hawary, Mahmoud M.; Francis, Isaac R.] Univ Michigan Hlth Syst, Univ Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. [Minter, Rebecca M.; Simeone, Diane M.] Univ Michigan Hlth Syst, Univ Hosp, Dept Surg, Ann Arbor, MI 48109 USA. [Simeone, Diane M.] Univ Michigan Hlth Syst, Univ Hosp, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Chari, Suresh T.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Hough, David M.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Fishman, Elliot K.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Lu, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Macari, Michael; Megibow, Alec J.] NYU, Med Ctr, Dept Radiol, New York, NY 10016 USA. [Miller, Frank H.] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Mortele, Koenraad J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Merchant, Nipun B.] Vanderbilt Univ, Dept Surg, Nashville, TN 37240 USA. [Tamm, Eric P.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Al-Hawary, MM (reprint author), Univ Michigan Hlth Syst, Univ Hosp, Dept Radiol, 1500 E Med Ctr Dr,Room B1 D502, Ann Arbor, MI 48109 USA. EM alhawary@med.umich.edu OI fishman, elliot/0000-0002-2567-1658 NR 39 TC 28 Z9 30 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2014 VL 146 IS 1 BP 291 EP + DI 10.1053/j.gastro.2013.11.004 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 276GF UT WOS:000328736000042 PM 24355035 ER PT S AU Parmigiani, G Boca, S Ding, J Trippa, L AF Parmigiani, Giovanni Boca, Simina Ding, Jie Trippa, Lorenzo BE Ochs, MF TI Statistical Tools and R Software for Cancer Driver Probabilities SO GENE FUNCTION ANALYSIS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Markov Chain Monte Carlo; Gene mutation; Cancer driver gene ID FALSE DISCOVERY RATES; COLORECTAL CANCERS; SOMATIC MUTATION; BAYESIAN-ANALYSIS; HUMAN BREAST AB This chapter provides a description and illustration of CancerMutationAnalysis and Cancer MutationMCMC, two open source R packages specifically designed for the analysis of somatic mutations in cancer genome studies, at both the gene and gene-set levels. C1 [Parmigiani, Giovanni; Ding, Jie; Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Boca, Simina] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Parmigiani, G (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 23 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-721-1; 978-1-62703-720-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1101 BP 113 EP 134 DI 10.1007/978-1-62703-721-1_7 D2 10.1007/978-1-62703-721-1 PG 22 WC Biochemical Research Methods; Genetics & Heredity; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Genetics & Heredity; Mathematical & Computational Biology GA BJH03 UT WOS:000328151100008 PM 24233780 ER PT J AU Saxon, AJ Browne, KC AF Saxon, Andrew J. Browne, Kendall C. TI Marijuana not ready for prime time as an analgesic SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material ID CANNABIS USE; ENDOCANNABINOID SYSTEM; ANXIETY DISORDERS; DOPAMINE RELEASE; NEUROPATHIC PAIN; DOUBLE-BLIND; DELTA-9-TETRAHYDROCANNABINOL; SCHIZOPHRENIA; PERFORMANCE; SYMPTOMS C1 [Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Browne, Kendall C.] Univ Calif San Diego, San Diego State Univ, San Diego Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. [Browne, Kendall C.] VA Puget Sound Hlth Care Syst, Psychol Serv, Seattle, WA 98108 USA. RP Saxon, AJ (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. EM Andrew.Saxon@va.gov NR 43 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2014 VL 36 IS 1 BP 4 EP 6 DI 10.1016/j.genhosppsych.2013.08.005 PG 3 WC Psychiatry SC Psychiatry GA 281OY UT WOS:000329112100005 PM 24176513 ER PT J AU Ganzini, L AF Ganzini, Linda TI Psychiatric evaluations for individuals requesting assisted death in Washington and Oregon should not be mandatory SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material ID DEPRESSION; SUICIDE; VIEWS; AID C1 [Ganzini, Linda] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Psychiat, Res Serv,Mental Hlth Div, Portland, OR 97201 USA. [Ganzini, Linda] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Psychiat, Res Serv,Hlth Serv Res & Dev Sect, Portland, OR 97201 USA. RP Ganzini, L (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Psychiat, Res Serv,Mental Hlth Div, Portland, OR 97201 USA. EM linda.ganzini@va.gov NR 10 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2014 VL 36 IS 1 BP 10 EP 12 DI 10.1016/j.genhosppsych.2013.08.006 PG 3 WC Psychiatry SC Psychiatry GA 281OY UT WOS:000329112100007 PM 24091255 ER PT J AU Huffman, JC DuBois, CM Healy, BC Boehm, JK Kashdan, TB Celano, CM Denninger, JW Lyubomirsky, S AF Huffman, Jeff C. DuBois, Christina M. Healy, Brian C. Boehm, Julia K. Kashdan, Todd B. Celano, Christopher M. Denninger, John W. Lyubomirsky, Sonja TI Feasibility and utility of positive psychology exercises for suicidal inpatients SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Gratitude; Hopelessness; Optimism; Positive psychology; Suicide ID FUTURE ORIENTATION; COUNTING BLESSINGS; DEPRESSED ADULTS; MENTAL-ILLNESS; SELF-ESTEEM; INTERVENTIONS; IDEATION; HOPELESSNESS; GRATITUDE; METAANALYSIS AB Objective: The objective was to assess the feasibility and acceptability of nine positive psychology exercises delivered to patients hospitalized for suicidal thoughts or behaviors, and to secondarily explore the relative impact of the exercises. Method: Participants admitted to a psychiatric unit for suicidal ideation or behavior completed daily positive psychology exercises while hospitalized. Likert-scale ratings of efficacy (optimism, hopelessness, perceived utility) and ease of completion were consolidated and compared across exercises using mixed models accounting for age, missing data and exercise order. Overall effects of exercise on efficacy and ease were also examined using mixed models. Results: Fifty-two (85.3%) of 61 participants completed at least one exercise, and 189/213 (88.7%) assigned exercises were completed. There were overall effects of exercise on efficacy (chi(2)=19.39; P=.013) but not ease of completion (chi(2)=11.64; P=.17), accounting for age, order and skipped exercises. Effect (Cohen's d) of exercise on both optimism and hopelessness was moderate for the majority of exercises. Exercises related to gratitude and personal strengths ranked highest. Both gratitude exercises had efficacy scores that were significantly (P=.001) greater than the lowest-ranked exercise (forgiveness). Conclusion: In this exploratory project, positive psychology exercises delivered to suicidal inpatients were feasible and associated with short-term gains in clinically relevant outcomes. (C) 2014 Elsevier Inc. All rights reserved. C1 [Huffman, Jeff C.; DuBois, Christina M.; Celano, Christopher M.; Denninger, John W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Huffman, Jeff C.; Healy, Brian C.; Celano, Christopher M.; Denninger, John W.] Harvard Univ, Sch Med, Boston, MA USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Boehm, Julia K.] Chapman Univ, Dept Psychol, Orange, CA USA. [Kashdan, Todd B.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Denninger, John W.] Benson Henry Inst Mind Body Med, Boston, MA USA. [Lyubomirsky, Sonja] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM jhuffman@partners.org FU US Centers for Disease Control and Prevention [R01-DP00336] FX Funding: This work was supported in part by grant R01-DP00336 from the US Centers for Disease Control and Prevention to Dr. Herbert Benson. There was no other funding source. NR 58 TC 22 Z9 22 U1 7 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2014 VL 36 IS 1 BP 88 EP 94 DI 10.1016/j.genhosppsych.2013.10.006 PG 7 WC Psychiatry SC Psychiatry GA 281OY UT WOS:000329112100019 PM 24230461 ER PT J AU Fahed, AC Roberts, AE Mital, S Lakdawala, NK AF Fahed, Akl C. Roberts, Amy E. Mital, Seema Lakdawala, Neal K. TI Heart Failure in Congenital Heart Disease A Confluence of Acquired and Congenital SO HEART FAILURE CLINICS LA English DT Article DE Heart failure; Congenital heart disease; Genomics; Adult ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; CELL-DERIVED CARDIOMYOCYTES; NOONAN-SYNDROME; CARDIOVASCULAR-DISEASE; DILATED CARDIOMYOPATHY; POSTGENOMIC-ERA; GREAT-ARTERIES; ADULTS; GENE; CARDIOTOXICITY AB Heart failure (HF) is a common cause of morbidity and mortality in congenital heart disease (CHD), with increasing prevalence because of improved treatment options and outcomes. Genetic factors and acquired postnatal factors in CHD might play a major role in the progression to HF. This article proposes 3 routes that lead to HF in CHD: rare monogenic entities that cause both CHD and HF; severe CHD lesions in which acquired hemodynamic effects of CHD or surgery result in HF; and, most commonly, a combined effect of complex genetics in overlapping pathways and acquired stressors caused by the primary lesion. C1 [Fahed, Akl C.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Fahed, Akl C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Roberts, Amy E.] Boston Childrens Hosp, Dept Cardiol, Div Genet, Boston, MA 02115 USA. [Mital, Seema] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Cardiol, Toronto, ON M5G 1X8, Canada. [Lakdawala, Neal K.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Lakdawala, Neal K.] Harvard Univ, Sch Med, VA Boston Hlth Care, Div Cardiol, Boston, MA 02115 USA. RP Lakdawala, NK (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM nlakdawala@partners.org FU NHLBI NIH HHS [U01 HL066582] NR 51 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JAN PY 2014 VL 10 IS 1 BP 219 EP + DI 10.1016/j.hfc.2013.09.017 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281FY UT WOS:000329086600019 PM 24275306 ER PT J AU Damiano, RJ Badhwar, V Acker, MA Veeragandham, RS Kress, DC Robertson, JO Sundt, TM AF Damiano, Ralph J., Jr. Badhwar, Vinay Acker, Michael A. Veeragandham, Ramesh S. Kress, David C. Robertson, Jason O. Sundt, Thoralf M. TI The CURE-AF trial: A prospective, multicenter trial of irrigated radiofrequency ablation for the treatment of persistent atrial fibrillation during concomitant cardiac surgery SO HEART RHYTHM LA English DT Article DE Arrhythmia surgery; Atrial fibrillation; Maze procedure; Radiofrequency ablation; Surgical ablation ID COX-MAZE PROCEDURE; FOLLOW-UP; TRANSPORT FUNCTION; CATHETER ABLATION; SURGICAL OUTCOMES; III PROCEDURE; EFFICACY; PREDICTORS; MANAGEMENT; SAFETY AB BACKGROUND Ablation technology has been introduced to replace the surgical incisions of the Cox-Maze procedure in order to simplify the operation. However, the efficacy of these ablation devices has not been prospectively evaluated. OBJECTIVE The purpose of this study was to examine the efficacy and safety of irrigated unipolar and bipolar radiofrequency ablation for the treatment of persistent and Long-standing persistent atrial fibrillation (AF) during concomitant cardiac surgical procedures. METHODS Between May 2007 and July 2011, 150 consecutive patients were enrolled at 15 U.S. centers. Patients were followed for 6 to 9 months, at which time a 24-hour Hotter recording and echocardiogram were obtained. Recurrent AF was defined as any atrial tachyarrhythmia (ATA) Lasting over 30 seconds on the Hotter monitor. The safety end-point was the percent of patients who suffered a major adverse event within 30 days of surgery. All patients underwent a biatrial Cox-Maze Lesion set. RESULTS Operative mortality was 4%, and there were 4 (3%) 30-day major adverse events. Overall freedom from ATAs was 66%, with 53% of patients free from ATAs and also off antiarrhythmic drugs at 6 to 9 months. Increased Left atrial diameter, shorter total ablation time, and an increasing number of concomitant procedures were associated with recurrent AF (P < .05). CONCLUSION Irrigated radiofrequency ablation for treatment of AF during cardiac surgery was associated with a low complication rate. No device-related complications occurred. The Cox-Maze Lesion set was effective at restoring sinus rhythm and had higher success rates in patients with smaller Left atrial diameters and longer ablation times. C1 [Damiano, Ralph J., Jr.; Robertson, Jason O.] Washington Univ, Sch Med, Div Cardiothorac Surg, St Louis, MO 63110 USA. [Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Acker, Michael A.] Hosp Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Veeragandham, Ramesh S.] John Muir Med Ctr, Dept Cardiothorac Surg, Concord, CA USA. [Kress, David C.] Aurora St Lukes Med Ctr, Dept Cardiovasc & Thorac Surg, Milwaukee, WI USA. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Damiano, RJ (reprint author), Washington Univ, Sch Med, Div Cardiothorac Surg, 660 S Euclid Ave,Campus Box 8234, St Louis, MO 63110 USA. EM damianor@wustl.edu FU Medtronic, Inc.; Medtronic; Thoratec, Inc.; AtriCure FX This study was supported by a grant from Medtronic, Inc. FDA approved as IDE Clinical Trial: ClinicalTrials.gov; NCT00431834 for permanent AF and NCT00506493 for persistent AF. Dr. Damiano receives consulting fees from AtriCure and Medtronic. Dr. Badhwar receives speaker fees from Medtronic. Dr. Acker receives consulting fees from Thoratec, Inc. Address reprint requests and correspondence: Dr. Ralph J. Damiano, Jr., Division of Cardiothoracic Surgery, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8234, St. Louis, MO 63110. E-mail address: damianor@wustl.edu. NR 24 TC 13 Z9 13 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2014 VL 11 IS 1 BP 39 EP 45 DI 10.1016/j.hrthm.2013.10.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281RR UT WOS:000329119200008 PM 24184028 ER PT J AU Cohen, AL Wenger, JB James-Todd, T Lamparello, BM Halprin, E Serdy, S Fan, SL Horowitz, GL Lim, KH Rana, S Takoudes, TC Wyckoff, JA Thadhani, R Karumanchi, SA Brown, FM AF Cohen, Allison L. Wenger, Julia B. James-Todd, Tamarra Lamparello, Brooke M. Halprin, Elizabeth Serdy, Shanti Fan, Shuling Horowitz, Gary L. Lim, Kee-Hak Rana, Sarosh Takoudes, Tamara C. Wyckoff, Jennifer A. Thadhani, Ravi Karumanchi, S. Ananth Brown, Florence M. TI The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes SO HYPERTENSION IN PREGNANCY LA English DT Article DE Angiogenesis; Diabetes; HbA1C; PlGF; Preeclampsia; sFlt1 ID PREGNANCY-INDUCED HYPERTENSION; ADVERSE NEONATAL OUTCOMES; GLYCEMIC CONTROL; NULLIPAROUS WOMEN; TYPE-1; MELLITUS; RETINOPATHY; DISEASE; SERUM AB Objective: To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes. Methods: Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N=159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th-75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N=139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data. Results: PE developed in 12% (N=19) and GHTN developed in 23% (N=37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35-40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19-7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27-34 weeks 15.18 (2.37-26.86), at 35-40 weeks 8.61(1.20-18.27), p <= 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE). Conclusions: Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE. C1 [Cohen, Allison L.; Lamparello, Brooke M.; Halprin, Elizabeth; Serdy, Shanti; Brown, Florence M.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Cohen, Allison L.; Halprin, Elizabeth; Serdy, Shanti; Fan, Shuling; Horowitz, Gary L.; Lim, Kee-Hak; Rana, Sarosh; Takoudes, Tamara C.; Karumanchi, S. Ananth; Brown, Florence M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wenger, Julia B.; Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [James-Todd, Tamarra] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wyckoff, Jennifer A.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Brown, FM (reprint author), Joslin Clin, Boston, MA USA. EM Florence.Brown@joslin.harvard.edu FU Department of Medicine Seed funds; Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard/MIT Health Sciences and Technology; Pfizer Inc.; Merck Co. FX This study was funded by Department of Medicine Seed funds to S. A. K. A. L. C received support from the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co. NR 34 TC 12 Z9 12 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 EI 1525-6065 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2014 VL 33 IS 1 BP 81 EP 92 DI 10.3109/10641955.2013.837175 PG 12 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 281WH UT WOS:000329131200008 PM 24354578 ER PT J AU Ruff, CT Bhatt, DL Steg, PG Gersh, BJ Alberts, MJ Hoffman, EB Ohman, EM Eagle, KA Lip, GYH Goto, S AF Ruff, Christian T. Bhatt, Deepak L. Steg, Ph. Gabriel Gersh, Bernard J. Alberts, Mark J. Hoffman, Elaine B. Ohman, E. Magnus Eagle, Kim A. Lip, Gregory Y. H. Goto, Shinya CA REACH Registry Investigators TI Long-term cardiovascular outcomes in patients with atrial fibrillation and atherothrombosis in the REACH Registry SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Atrial fibrillation; Atherosclerosis; Anticoagulation; Vascular disease ID PERCUTANEOUS CORONARY INTERVENTION; VON-WILLEBRAND-FACTOR; SOLUBLE P-SELECTIN; EURO HEART SURVEY; RISK-FACTORS; MYOCARDIAL-INFARCTION; PREDICTING STROKE; EVENT RATES; ANTITHROMBOTIC THERAPY; DIASTOLIC DYSFUNCTION AB Background: Patients with atrial fibrillation (AF) are at increased risk of thromboembolic events. The long-term prognostic implications of AF in patients with atherothrombosis are unknown. Methods: We compared 4-year CV outcomes in patients with and without a history of AF recorded at their baseline visit in the REACH Registry, an international, prospective cohort of patients with established atherosclerotic arterial disease (CAD, CVD, PAD) or at least 3 risk factors (RFO). Results: AF status and 4 year follow-up data were available on 44,518 patients. The prevalence of AF at baseline was 10.3% (n = 4582). Overall, patients with AF had approximately a 2-fold increase in the composite of CV death, MI, or stroke compared with patients without AF after adjustment for age, gender, prior ischemic event, vascular disease, congestive heart failure, diabetes, smoking, body mass index, region, aspirin and statin use (18.9% vs. 9.4%, p < 0.0001). This increased risk was observed both in patients with established atherothrombosis (CAD: 15.5% vs. 8.0%, p = 0.0001; CVD: 23.6% vs. 13.6%, p < 0.0001; PAD: 24.3% vs. 13.5%, p = 0.089) and those with multiple risk factors (RFO: 12.1% vs. 5.9%, p = 0.017). Only 52% of patients with a history of AF at baseline were receiving anticoagulation at 4 years. Conclusions: Patients with a history of both AF and atherothrombosis have particularly high long-term CV risk. Despite this increased risk, almost half of all patients with AF do not receive guideline recommended anticoagulation, highlighting an important public health priority. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Ruff, Christian T.; Hoffman, Elaine B.] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Sch Med, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA. [Steg, Ph. Gabriel] Univ Paris 07, AP HP, INSERM U698, Paris, France. [Gersh, Bernard J.] Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN USA. [Alberts, Mark J.] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL USA. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Lip, Gregory Y. H.] Univ Birmingham, Ctr Cardiovasc Sci, City Hosp, Birmingham, W Midlands, England. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Goto, Shinya] Tokai Univ, Sch Med, Metab Dis Ctr, Kanagawa 2591100, Japan. RP Ruff, CT (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Offices, Boston, MA 02115 USA. EM cruff@partners.org OI Bhatt, Deepak/0000-0002-1278-6245 FU AstraZeneca; Merck; Amarin; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company; FlowCo; PLx Pharma; Takeda; Servier; EKR Therapeutics; AGA Medical; Lundbeck; Athena Neurosciences; CV Therapeutics; Daiichi Sankyo; Datascope; Eli Lilly; Marquet; Sanofi-Aventis; Schering-Plough; Blue Cross Blue Shield of Michigan; National Institutes of Health (NIH); Mardigian Foundation Varbedian Fund; GORE; Hewlett Foundation; Waksman Foundation (Tokyo, Japan); World Heart Federation FX Dr. Ruff-Research grants from AstraZeneca, Merck; Consulting for Alere, Beckman Coulter and Daiichi Sankyo. Dr. Bhatt-Advisory Board: Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association GetWith The Guidelines Steering Committee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); Other: Senior Associate Editor, Journal of Invasive Cardiology; Data Monitoring Committees: Duke Clinical Research Institute; Harvard Clinical Research Institute; Mayo Clinic; Population Health Research Institute; Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. Dr. Steg-Research grant from Servier; Participated in consultancy or advisory board for Eisai, Amgen, Astellas, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo-Lilly, GlaxoSmithKline, Merck, Pfizer, Roche, The Medicines Company, AstraZeneca, Sanofi-Aventis, Servier; Stockholder in Aterovax. Dr. Gersh-Consulting or data safety monitoring board for Ortho-McNeil Janssen Scientific Affairs, Amorcyte, GE Healthcare, St. Jude Medical, Medispec Limited, Merck, Boston Scientific. Dr. Alberts-Research grants from Merck, EKR Therapeutics, AGA Medical, Lundbeck; Speaker with honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis, Genentech, EKR Therapeutics; Speaker with honoraria from Boehringer Ingelheim, Janssen, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, EKR Therapeutics, Lundbeck; Royalty payments from Athena Neurosciences. Dr. Hoffman-none. Dr. Ohman-Research grants from Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Datascope, Eli Lilly, Marquet, Sanofi-Aventis, Schering-Plough, and The Medicines Company; Consulting or other services for Abiomed, AstraZeneca, CV Therapeutics, Datascope, Gilead Sciences, Liposcience, Marquet, Northpoint Domain, Pozen, Response Biomedical, Sanofi-Aventis and The Medicines Company. Dr. Eagle-Grant/research support from Bristol-Myers Squibb, Blue Cross Blue Shield of Michigan, the National Institutes of Health (NIH), Sanofi-Aventis, the Mardigian Foundation Varbedian Fund, GORE, and the Hewlett Foundation; Consultant for the NIH National Heart, Lung, and Blood Institute, Sanofi-Aventis, and the RobertWood Johnson Foundation. Dr Lip-Consulting for Bayer, Astellas, Merck, AstraZeneca, Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Biotronik, Portola and Boehringer Ingelheim; Speakers Bureau for Bayer, Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim. Dr. Goto-Research grants from Sanofi-Aventis, Eisai, Boehringer Ingelheim, Otsuka, Daiichi Sankyo; Consulting for Eisai, Sanofi-Aventis, Otsuka, Bayer, Novartis, AstraZeneca, Asteras, Pfizer, Medtronics-Japan, Tanabe-Mitsubishi, Takeda, Daiichi Sankyo, Mochida, MSD. Sources of funding/support The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and theWaksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. NR 44 TC 16 Z9 17 U1 0 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD JAN 1 PY 2014 VL 170 IS 3 BP 413 EP 418 DI 10.1016/j.ijcard.2013.11.030 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281TO UT WOS:000329124100034 PM 24321327 ER PT J AU Wallentin, L Becker, RC Cannon, CP Held, C Himmelmann, A Husted, S James, SK Katus, HS Mahaffey, KW Pieper, KS Storey, RF Steg, PG Harrington, RA AF Wallentin, Lars Becker, Richard C. Cannon, Christopher P. Held, Claes Himmelmann, Anders Husted, Steen James, Stefan K. Katus, Hugo S. Mahaffey, Kenneth W. Pieper, Karen S. Storey, Robert F. Steg, Philippe Gabriel Harrington, Robert A. TI Review of the accumulated PLATO documentation supports reliable and consistent superiority of ticagrelor over clopidogrel in patients with acute coronary syndrome Commentary on: DiNicolantonio JJ, Tomek A, Inactivations, deletions, non-adjudications, and downgrades of clinical endpoints on ticagrelor: Serious concerns over the reliability of the PLATO trial, International Journal of Cardiology, 2013 SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Acute coronary syndrome; Myocardial infarction; Platelet inhibition; Clopidogrel; Ticagrelor; Clinical trial ID RANDOMIZED PLATELET INHIBITION; OUTCOMES TRIAL; ASSOCIATION; MANAGEMENT; INSIGHTS; 1ST C1 [Wallentin, Lars; Held, Claes; James, Stefan K.] Uppsala Univ, Dept Med Sci, SE-75237 Uppsala, Sweden. [Wallentin, Lars; Held, Claes; James, Stefan K.] Uppsala Univ, Uppsala Clin Res Ctr, SE-75237 Uppsala, Sweden. [Becker, Richard C.; Pieper, Karen S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Himmelmann, Anders] AstraZeneca Res & Dev, Molndal, Sweden. [Husted, Steen] Hosp Unit West, Dept Med, Herning Holstbro, Denmark. [Katus, Hugo S.] Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany. [Mahaffey, Kenneth W.; Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Steg, Philippe Gabriel] INSERM, Unite 698, Paris, France. [Steg, Philippe Gabriel] Dept Hosp Univ FIRE, Hop Bichat, AP HP, Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. RP Wallentin, L (reprint author), Uppsala Univ, Uppsala Clin Res Ctr, SE-75237 Uppsala, Sweden. EM Lars.Wallentin@ucr.uu.se RI Katus, Hugo/P-1712-2016 NR 24 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD JAN 1 PY 2014 VL 170 IS 3 BP E59 EP E62 DI 10.1016/j.ijcard.2013.11.003 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281TO UT WOS:000329124100002 PM 24299581 ER PT J AU Wallner, PE Anscher, MS Barker, CA Bassetti, M Bristow, RG Cha, YI Dicker, AP Formenti, SC Graves, EE Hahn, SM Hei, TK Kimmelman, AC Kirsch, DG Kozak, KR Lawrence, TS Marples, B McBride, WH Mikkelsen, RB Park, CC Weidhaas, JB Zietman, AL Steinberg, M AF Wallner, Paul E. Anscher, Mitchell S. Barker, Christopher A. Bassetti, Michael Bristow, Robert G. Cha, Yong I. Dicker, Adam P. Formenti, Silvia C. Graves, Edward E. Hahn, Stephen M. Hei, Tom K. Kimmelman, Alec C. Kirsch, David G. Kozak, Kevin R. Lawrence, Theodore S. Marples, Brian McBride, William H. Mikkelsen, Ross B. Park, Catherine C. Weidhaas, Joanne B. Zietman, Anthony L. Steinberg, Michael TI Current Status and Recommendations for the Future of Research, Teaching, and Testing in the Biological Sciences of Radiation Oncology: Report of the American Society for Radiation Oncology Cancer Biology/Radiation Biology Task Force, Executive Summary SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article AB In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective of relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report. (C) 2014 Elsevier Inc. C1 [Wallner, Paul E.] 21st Century Oncol, LLC, Bethesda, MD 20814 USA. [Wallner, Paul E.; Mikkelsen, Ross B.] Amer Board Radiol, Bethesda, MD USA. [Anscher, Mitchell S.; Mikkelsen, Ross B.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. [Barker, Christopher A.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Bassetti, Michael] Univ Wisconsin, Dept Human Oncol, Carbone Canc Ctr, Madison, WI USA. [Bristow, Robert G.] Univ Toronto, Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada. [Bristow, Robert G.] Univ Toronto, Princess Margaret Canc Ctr, Dept Med Biophys, Toronto, ON, Canada. [Cha, Yong I.] Norton Canc Ctr, Dept Radiat Oncol, Louisville, KY USA. [Dicker, Adam P.] Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Formenti, Silvia C.] NYU, Dept Radiat Oncol, New York, NY USA. [Graves, Edward E.] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. [Graves, Edward E.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Hahn, Stephen M.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Hei, Tom K.] Columbia Univ, Ctr Radiat Res, New York, NY USA. [Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Kirsch, David G.] Duke Univ, Dept Radiat Oncol, Durham, NC USA. [Kozak, Kevin R.] Univ Wisconsin, Dept Human Oncol, Madison, WI 53706 USA. [Lawrence, Theodore S.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Marples, Brian] Oakland Univ, Dept Radiat Oncol, Oakland, CA USA. [McBride, William H.; Steinberg, Michael] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA. [Park, Catherine C.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Weidhaas, Joanne B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Wallner, PE (reprint author), 21st Century Oncol, LLC, 5013 Cedar Croft La, Bethesda, MD 20814 USA. EM pwallner@theabr.org NR 0 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2014 VL 88 IS 1 BP 11 EP 17 DI 10.1016/j.ijrobp.2013.09.040 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 277ZN UT WOS:000328857900005 PM 24246724 ER PT J AU Golden, DW Spektor, A Rudra, S Ranck, MC Krishnan, MS Jimenez, RB Viswanathan, AN Koshy, M Howard, AR Chmura, SJ AF Golden, Daniel W. Spektor, Alexander Rudra, Sonali Ranck, Mark C. Krishnan, Monica S. Jimenez, Rachel B. Viswanathan, Akila N. Koshy, Matthew Howard, Andrew R. Chmura, Steven J. TI Radiation Oncology Medical Student Clerkship: Implementation and Evaluation of a Bi-institutional Pilot Curriculum SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID EDUCATION; ROTATION AB Purpose: To develop and evaluate a structured didactic curriculum to complement clinical experiences during radiation oncology clerkships at 2 academic medical centers. Methods and Materials: A structured didactic curriculum was developed to teach fundamentals of radiation oncology and improve confidence in clinical competence. Curriculum lectures included: (1) an overview of radiation oncology (history, types of treatments, and basic clinic flow); (2) fundamentals of radiation biology and physics; and (3) practical aspects of radiation treatment simulation and planning. In addition, a hands-on dosimetry session taught students fundamentals of treatment planning. The curriculum was implemented at 2 academic departments in 2012. Students completed anonymous evaluations using a Likert scale to rate the usefulness of curriculum components (1 = not at all, 5 = extremely). Likert scores are reported as (median [interquartile range]). Results: Eighteen students completed the curriculum during their 4-week rotation (University of Chicago n=13, Harvard Longwood Campus n=5). All curriculum components were rated as extremely useful: introduction to radiation oncology (5 [4-5]); radiation biology and physics (5 [5-5]); practical aspects of radiation oncology (5 [4-5]); and the treatment planning session (5 [5-5]). Students rated the curriculum as "quite useful" to "extremely useful" (1) to help students understand radiation oncology as a specialty; (2) to increase student comfort with their specialty decision; and (3) to help students with their future transition to a radiation oncology residency. Conclusions: A standardized curriculum for medical students completing a 4-week radiation oncology clerkship was successfully implemented at 2 institutions. The curriculum was favorably reviewed. As a result of completing the curriculum, medical students felt more comfortable with their specialty decision and better prepared to begin radiation oncology residency. (C) 2014 Elsevier Inc. C1 [Golden, Daniel W.; Rudra, Sonali; Ranck, Mark C.; Koshy, Matthew; Howard, Andrew R.; Chmura, Steven J.] Univ Chicago, Pritzker Sch Med, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Spektor, Alexander; Krishnan, Monica S.; Jimenez, Rachel B.; Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Spektor, Alexander; Krishnan, Monica S.; Jimenez, Rachel B.; Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Golden, DW (reprint author), Univ Chicago, Pritzker Sch Med, Dept Radiat & Cellular Oncol, 5758 South Maryland Ave,Mail Code 9006, Chicago, IL 60637 USA. EM dgolden@radonc.uchicago.edu FU Radiologic Society of North America FX D.W.G. received grants from the Radiologic Society of North America during the conduct of the study. NR 22 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2014 VL 88 IS 1 BP 45 EP 50 DI 10.1016/j.ijrobp.2013.10.041 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 277ZN UT WOS:000328857900010 PM 24331650 ER PT J AU Truong, PT Sadek, BT Lesperance, MF Alexander, CS Shenouda, M Raad, RA Taghian, AG AF Truong, Pauline T. Sadek, Betro T. Lesperance, Maria F. Alexander, Cheryl S. Shenouda, Mina Raad, Rita Abi Taghian, Alphonse G. TI Is Biological Subtype Prognostic of Locoregional Recurrence Risk in Women With pT1-2N0 Breast Cancer Treated With Mastectomy? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID INTERNATIONAL EXPERT CONSENSUS; POSTMASTECTOMY RADIATION; ADJUVANT CHEMOTHERAPY; CONSERVING THERAPY; LOCAL RECURRENCE; RADIOTHERAPY; EXPRESSION; CARCINOMA; RECEPTOR; TRASTUZUMAB AB Purpose: To examine locoregional and distant recurrence (LRR and DR) in women with pT1-2N0 breast cancer according to approximated subtype and clinicopathologic characteristics. Methods and Materials: Two independent datasets were pooled and analyzed. The study participants were 1994 patients with pT1-2N0M0 breast cancer, treated with mastectomy without radiation therapy. The patients were classified into 1 of 5 subtypes: luminal A (ER+ or PR+/HER 2-/grade 1-2, n=1202); luminal B (ER+ or PR+/HER 2-/grade 3, n=294); luminal HER 2 (ER+ or PR+/HER 2+, n=221); HER 2 (ER-/PR-/HER 2+, n=105) and triple-negative breast cancer (TNBC) (ER-/PR-/HER 2-, n=172). Results: The median follow-up time was 4.3 years. The 5-year Kaplan-Meier (KM) LRR were 1.8% in luminal A, 3.1% in luminal B, 1.7% in luminal HER 2, 1.9% in HER 2, and 1.9% in TNBC cohorts (P = .81). The 5-year KM DR was highest among women with TNBC: 1.8% in luminal A, 5.0% in luminal B, 2.4% in luminal HER 2, 1.1% in HER 2, and 9.6% in TNBC cohorts (P<.001). Among 172 women with TNBC, the 5-year KM LRR were 1.3% with clear margins versus 12.5% with close or positive margins (PZ=.04). On multivariable analysis, factors that conferred higher LRR risk were tumors >2 cm, lobular histology, and close/positive surgical margins. Conclusions: The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes. Among the subtypes, TNBC conferred the highest risk of DR and an elevated risk of LRR in the presence of positive or close margins. Our data suggest that although subtype alone cannot be used as the sole criterion to offer postmastectomy radiation therapy, it may reasonably be considered in conjunction with other clinicopathologic factors including tumor size, histology, and margin status. Larger cohorts and longer follow-up times are needed to define which women with node-negative disease have high postmastectomy LRR risks in contemporary practice. (C) 2014 Elsevier Inc. C1 [Truong, Pauline T.; Lesperance, Maria F.] Univ British Columbia, British Columbia Canc Agcy, Vancouver Isl Ctr, Radiat Therapy Program, Victoria, BC, Canada. [Truong, Pauline T.; Alexander, Cheryl S.] Univ British Columbia, British Columbia Canc Agcy, Vancouver Isl Ctr, Breast Canc Outcomes Unit, Victoria, BC, Canada. [Sadek, Betro T.; Shenouda, Mina; Raad, Rita Abi; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Truong, PT (reprint author), BC Canc Agcy, Vancouver Isl Ctr, 2410 Lee Ave, Victoria, BC V8R 6V5, Canada. EM ptruong@bccancer.bc.ca RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 35 TC 10 Z9 12 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2014 VL 88 IS 1 BP 57 EP 64 DI 10.1016/j.ijrobp.2013.09.024 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 277ZN UT WOS:000328857900012 PM 24161421 ER PT J AU Grosse, N Fontana, AO Hug, EB Lomax, A Coray, A Augsburger, M Paganetti, H Sartori, AA Pruschy, M AF Grosse, Nicole Fontana, Andrea O. Hug, Eugen B. Lomax, Antony Coray, Adolf Augsburger, Marc Paganetti, Harald Sartori, Alessandro A. Pruschy, Martin TI Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID STRAND-BREAK REPAIR; PAUL-SCHERRER-INSTITUTE; DNA-DAMAGE; PATHWAY CHOICE; X-RAYS; RADIATION; CYCLE; BEAM; RADIOTHERAPY; SURVIVAL AB Purpose: To investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation. Methods and Materials: The DNA repair and cell survival endpoints in wild-type, homologous recombination (HR)-deficient, and nonhomologous end-joining-deficient cells were analyzed after irradiation with clinically relevant, low-linear energy transfer (LET) protons and 200-keV photons. Results: All cell lines were more sensitive to proton irradiation compared with photon irradiation, despite no differences in the induction of DNA breaks. Interestingly, HR-deficient cells and wildtype cells with small interfering RNA-down-regulated Rad51 were markedly hypersensitive to proton irradiation, resulting in an increased relative biological effectiveness in comparison with the relative biological effectiveness determined in wild-type cells. In contrast, lack of nonhomologous end-joining did not result in hypersensitivity toward proton irradiation. Repair kinetics of DNA damage in wild-type cells were equal after both types of irradiation, although proton irradiation resulted in more lethal chromosomal aberrations. Finally, repair kinetics in HR-deficient cells were significantly delayed after proton irradiation, with elevated amounts of residual gamma H2AX foci after irradiation. Conclusion: Our data indicate a differential quality of DNA damage by proton versus photon irradiation, with a specific requirement for homologous recombination for DNA repair and enhanced cell survival. This has potential relevance for clinical stratification of patients carrying mutations in the DNA damage response pathways. (C) 2014 Elsevier Inc. C1 [Grosse, Nicole; Fontana, Andrea O.; Augsburger, Marc; Pruschy, Martin] Univ Zurich Hosp, Lab Mol Radiobiol, CH-8091 Zurich, Switzerland. [Hug, Eugen B.; Lomax, Antony; Coray, Adolf] Paul Scherrer Inst, Ctr Proton Therapy, Villigen, Switzerland. [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Sartori, Alessandro A.] Univ Zurich, Inst Mol Canc Res, Zurich, Switzerland. RP Pruschy, M (reprint author), Univ Zurich Hosp, Lab Mol Radiobiol, Raemistr 100, CH-8091 Zurich, Switzerland. EM martin.pruschy@usz.ch OI Sartori, Alessandro/0000-0003-2770-0333 FU Swiss Cancer League; University of Zurich; Swiss National Science Foundation; Vontobel Foundation FX This study was supported by grants from the Swiss Cancer League (to M. P.), the University of Zurich (to E. B. H.), the Swiss National Science Foundation, and the Vontobel Foundation (to A. A. S.) NR 34 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2014 VL 88 IS 1 BP 175 EP 181 DI 10.1016/j.ijrobp.2013.09.041 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 277ZN UT WOS:000328857900028 PM 24239385 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI We Need Better Figures! Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2014 VL 88 IS 1 BP 236 EP 236 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 277ZN UT WOS:000328857900038 PM 24475500 ER PT J AU Lakdawalla, DN Jena, AB Doctor, JN AF Lakdawalla, Darius N. Jena, Anupam B. Doctor, Jason N. TI Careful Use of Science to Advance the Debate on the UK Cancer Drugs Fund SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID LIFE; END C1 [Lakdawalla, Darius N.; Doctor, Jason N.] Univ So Calif, Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu OI Lakdawalla, Darius/0000-0001-5934-8042 FU NIA NIH HHS [RC4 AG039036, RC4AG039036]; NIH HHS [1DP5OD017897-01, DP5 OD017897] NR 8 TC 2 Z9 2 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 2014 VL 311 IS 1 BP 25 EP 26 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 282HN UT WOS:000329161400012 PM 24381964 ER PT J AU Dysken, MW Sano, M Asthana, S Vertrees, JE Pallaki, M Llorente, M Love, S Schellenberg, GD McCarten, JR Malphurs, J Prieto, S Chen, PJ Loreck, DJ Trapp, G Bakshi, RS Mintzer, JE Heidebrink, JL Vidal-Cardona, A Arroyo, LM Cruz, AR Zachariah, S Kowall, NW Chopra, MP Craft, S Thielke, S Turvey, CL Woodman, C Monnell, KA Gordon, K Tomaska, J Segal, Y Peduzzi, PN Guarino, PD AF Dysken, Maurice W. Sano, Mary Asthana, Sanjay Vertrees, Julia E. Pallaki, Muralidhar Llorente, Maria Love, Susan Schellenberg, Gerard D. McCarten, J. Riley Malphurs, Julie Prieto, Susana Chen, Peijun Loreck, David J. Trapp, George Bakshi, Rajbir S. Mintzer, Jacobo E. Heidebrink, Judith L. Vidal-Cardona, Ana Arroyo, Lillian M. Cruz, Angel R. Zachariah, Sally Kowall, Neil W. Chopra, Mohit P. Craft, Suzanne Thielke, Stephen Turvey, Carolyn L. Woodman, Catherine Monnell, Kimberly A. Gordon, Kimberly Tomaska, Julie Segal, Yoav Peduzzi, Peter N. Guarino, Peter D. TI Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease The TEAM-AD VA Cooperative Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; NURSING-HOME PLACEMENT; CLINICAL-TRIALS; CO-MORBIDITY; DOUBLE-BLIND; MODERATE; METAANALYSIS; DEMENTIA; SUPPLEMENTATION; GALANTAMINE AB IMPORTANCE Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS Over the mean (SD) follow-up of 2.27 (1.22) years, participants receiving alpha tocopherol had slower decline than those receiving placebo as measured by the ADCS-ADL. The change translates into a delay in clinical progression of 19% per year compared with placebo (approximately 6.2 months over the follow-up period). Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations" with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). [GRAPHICS] . CONCLUSIONS AND RELEVANCE Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. C1 [Dysken, Maurice W.; Love, Susan; McCarten, J. Riley; Tomaska, Julie; Segal, Yoav] Minneapolis VA Hlth Care Syst, Minneapolis, MN 55417 USA. [Sano, Mary] James J Peters VA Med Res Ctr, New York, NY USA. [Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Vertrees, Julia E.] Clin Res Pharm Coordinating Ctr, Cooperat Studies Program, Albuquerque, NM USA. [Pallaki, Muralidhar; Chen, Peijun] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Pallaki, Muralidhar; Chen, Peijun] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Llorente, Maria] Washington DC VA Med Ctr, Washington, DC USA. [Schellenberg, Gerard D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Malphurs, Julie; Prieto, Susana] Miami VA Healthcare Syst, Miami, FL USA. [Loreck, David J.] VA Maryland Healthcare Syst, Baltimore, MD USA. [Loreck, David J.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Trapp, George; Bakshi, Rajbir S.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Dept Hlth Studies, Charleston, SC USA. [Mintzer, Jacobo E.] Roper St Francis Healthcare, Charleston, SC USA. [Heidebrink, Judith L.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Vidal-Cardona, Ana; Arroyo, Lillian M.] VA Caribbean Healthcare Syst, San Juan, PR USA. [Cruz, Angel R.; Zachariah, Sally] Bay Pines VA Healthcare Syst, Bay Pines, FL USA. [Kowall, Neil W.; Chopra, Mohit P.] VA Boston Healthcare Syst, Boston, MA USA. [Craft, Suzanne; Thielke, Stephen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Craft, Suzanne; Thielke, Stephen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Turvey, Carolyn L.; Woodman, Catherine] Iowa City VA Med Ctr, Iowa City, IA USA. [Turvey, Carolyn L.; Woodman, Catherine] Univ Iowa, Iowa City, IA USA. [Monnell, Kimberly A.; Gordon, Kimberly] WG Bill Hefner VA Med Ctr, Salisbury, NC USA. [Peduzzi, Peter N.; Guarino, Peter D.] VA Connecticut Healthcare Syst, Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. [Peduzzi, Peter N.; Guarino, Peter D.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Dysken, MW (reprint author), Minneapolis VA Hlth Care Syst, GRECC Program 11G, 1 Vet Dr, Minneapolis, MN 55417 USA. EM maurice.dysken@va.gov RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU Veterans Affairs Cooperative Studies Program, Office of Research and Development, Clinical Science RD; Arista Industries FX VA TEAM-AD was funded by the Veterans Affairs Cooperative Studies Program, Office of Research and Development, Clinical Science R&D. Forest Research Institute, a Division of Forest Laboratories, donated the memantine and matching placebo tablets. DSM Nutritional Products donated the DL-alpha-tocopheryl acetate oil and funding for the purchase of the soybean oil from Arista Industries. NR 39 TC 107 Z9 107 U1 11 U2 56 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 2014 VL 311 IS 1 BP 33 EP 44 DI 10.1001/jama.2013.282834 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 282HN UT WOS:000329161400016 PM 24381967 ER PT J AU Penniston, JT Padanyi, R Paszty, K Varga, K Hegedus, L Enyedi, A AF Penniston, John T. Padanyi, Rita Paszty, Katalin Varga, Karolina Hegedues, Luca Enyedi, Agnes TI Apart from its known function, the plasma membrane Ca2+ ATPase can regulate Ca2+ signaling by controlling phosphatidylinositol 4,5-bisphosphate levels SO JOURNAL OF CELL SCIENCE LA English DT Article DE Plasma membrane Ca2+ ATPase; PMCA; Phosphatidylinositol 4,5,-bisphosphate; PtdIns(4,5)P-2; Ca2+ signaling; Molecular dynamics simulation ID CALMODULIN-BINDING DOMAIN; CA2+-ATPASE ISOFORM 2; HUMAN T-CELLS; CALCIUM-PUMP; CA-2+ PUMP; PROTEIN INTERACTIONS; CRYSTAL-STRUCTURE; K+ CHANNEL; PIP2; ACTIVATION AB Plasma membrane Ca2+ ATPases (PMCAs, also known as ATP2B1-ATP2B4) are known targets of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2], but if and how they control the PtdIns(4,5)P-2 pool has not been considered. We demonstrate here that PMCAs protect PtdIns(4,5) P-2 in the plasma membrane from hydrolysis by phospholipase C (PLC). Comparison of active and inactive PMCAs indicates that the protection operates by two mechanisms; one requiring active PMCAs, the other not. It appears that the mechanism requiring activity is the removal of the Ca2+ required for sustained PLC activity, whereas the mechanism not requiring activity is PtdIns(4,5) P-2 binding. We show that in PMCA overexpressing cells, PtdIns(4,5) P-2 binding can lead to less inositol 1,4,5-triphosphate (InsP(3)) and diminished Ca2+ release from intracellular Ca2+ pools. Inspection of a homology model of PMCA suggests that PMCAs have a conserved cluster of basic residues forming a 'blue collar' at the interface between the membrane core and the cytoplasmic domains. By molecular dynamics simulation, we found that the blue collar forms four binding pockets for the phosphorylated inositol head group of PtdIns(4,5) P-2; these pockets bind PtdIns(4,5) P-2 strongly and frequently. Our studies suggest that by having the ability to bind PtdIns(4,5) P-2, PMCAs can control the accessibility of PtdIns(4,5) P-2 for PLC and other PtdIns(4,5) P-2-mediated processes. C1 [Penniston, John T.; Varga, Karolina; Hegedues, Luca; Enyedi, Agnes] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Mol Pharmacol Res, H-1025 Budapest, Hungary. [Penniston, John T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Padanyi, Rita; Enyedi, Agnes] Hungarian Natl Blood Transfus Serv, H-1113 Budapest, Hungary. [Paszty, Katalin] Hungarian Acad Sci, Mol Biophys Res Grp, H-1051 Budapest, Hungary. [Paszty, Katalin] Semmelweis Univ, Dept Biophys, H-1051 Budapest, Hungary. RP Enyedi, A (reprint author), Hungarian Acad Sci, Res Ctr Nat Sci, Inst Mol Pharmacol Res, H-1025 Budapest, Hungary. EM enyedi@biomembrane.hu OI Paszty, Katalin/0000-0003-2457-8555 FU Hungarian Scientific Research Fund (OTKA) [CK 80283, K 101064]; Hungarian National Development Agency [TRANSRAT KMR_12-1-2012-0112] FX This work was supported by grants from the Hungarian Scientific Research Fund (OTKA) [grant numbers CK 80283 and K 101064 to A. E.]; and Hungarian National Development Agency [grant number TRANSRAT KMR_12-1-2012-0112 to K.P.]. NR 72 TC 9 Z9 9 U1 2 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2014 VL 127 IS 1 BP 72 EP 84 DI 10.1242/jcs.132548 PG 13 WC Cell Biology SC Cell Biology GA 281SY UT WOS:000329122500009 PM 24198396 ER PT J AU Dehaes, M Aggarwal, A Lin, PY Fortuno, CR Fenoglio, A Roche-Labarbe, N Soul, JS Franceschini, MA Grant, PE AF Dehaes, Mathieu Aggarwal, Alpna Lin, Pei-Yi Fortuno, C. Rosa Fenoglio, Angela Roche-Labarbe, Nadege Soul, Janet S. Franceschini, Maria Angela Grant, P. Ellen TI Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral blood circulation; cerebral hemoglobin oxygen saturation; cerebral metabolic rate of oxygen consumption; near infrared spectroscopy; neonatal hypoxic ischemic encephalopathy; therapeutic hypothermia ID NEAR-INFRARED SPECTROSCOPY; BLOOD-VOLUME; BRAIN-INJURY; CARDIOPULMONARY BYPASS; IN-VIVO; NEWBORNS; FLOW; MRI; HEMODYNAMICS; CONSUMPTION AB Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization. C1 [Dehaes, Mathieu; Aggarwal, Alpna; Fenoglio, Angela; Grant, P. Ellen] Boston Childrens Hosp, Div Newborn Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. [Dehaes, Mathieu; Aggarwal, Alpna] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lin, Pei-Yi; Roche-Labarbe, Nadege; Franceschini, Maria Angela; Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lin, Pei-Yi; Roche-Labarbe, Nadege; Franceschini, Maria Angela; Grant, P. Ellen] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Fortuno, C. Rosa; Soul, Janet S.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Fortuno, C. Rosa; Soul, Janet S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Grant, P. Ellen] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Dehaes, M (reprint author), Boston Childrens Hosp, Div Newborn Med, 300 Longwood Ave, Boston, MA 02115 USA. EM mathieu.dehaes@childrens.harvard.edu; ellen.grant@childrens.harvard.edu RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 FU NIH/NICHD [R21-HD058725, R01-HD042908]; NIH/NCRR [P41-RR14075]; Isabelle and Leonard H Goldenson Biomedical Research Foundation; William Randolph Hearst Foundation FX The authors would like to acknowledge funding from NIH/NICHD R21-HD058725 (PEG), R01-HD042908 (MAF), and NIH/NCRR P41-RR14075 (BRR) as well as funding from the Isabelle and Leonard H Goldenson Biomedical Research Foundation (MD) and the William Randolph Hearst Foundation (MD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 57 TC 23 Z9 25 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2014 VL 34 IS 1 BP 87 EP 94 DI 10.1038/jcbfm.2013.165 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 282YK UT WOS:000329210700011 PM 24064492 ER PT J AU Shen, Q Du, F Huang, SL Duong, TQ AF Shen, Qiang Du, Fang Huang, Shiliang Duong, Timothy Q. TI Effects of cerebral ischemic and reperfusion on T-2*-weighted MRI responses to brief oxygen challenge SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CBF; diffusion; middle cerebral artery occlusion; mismatch; perfusion ID BLOOD-FLOW; NORMOBARIC HYPEROXIA; FUNCTIONAL MRI; QUANTITATIVE PERFUSION; ANESTHETIZED RATS; FOCAL ISCHEMIA; TISSUE FATE; BOLD FMRI; STROKE; DIFFUSION AB This study characterized the effects of cerebral ischemia and reperfusion on T-2*-weighted magnetic resonance image (MRI) responses to brief oxygen challenge (OC) in transient (60 minutes) cerebral ischemia in rats. During occlusion, the ischemic core tissue showed no significant OC response, whereas the perfusion-diffusion mismatch tissue showed markedly higher percent changes relative to normal tissue. After reperfusion, much of the pixels with initial exaggerated OC responses showed normal OC responses, and the majority of these tissues were salvaged as defined by endpoint T-2 MRI. The initial core pixels showed exaggerated OC responses after reperfusion, but the majority of the core pixels eventually became infarct, suggesting exaggerated OC responses do not necessarily reflect salvageable tissue. Twenty-four hours after stroke, basal T-1 increased in the ischemic core. Oxygen challenge decreased T-1 significantly in the core, indicative of the substantial increases in dissolved oxygen in the core as the result of hyperperfusion. We concluded that exaggerated T-2*-weighted MRI responses to OC offer useful insight in ischemic tissue fates. However, exaggerated OC pixels are not all salvageable, and they exhibited complex dynamics depending on reperfusion status, hyperperfusion, and edema effects. C1 [Shen, Qiang; Du, Fang; Huang, Shiliang; Duong, Timothy Q.] Dept Res Imaging Inst, San Antonio, TX USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas San Antonio, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78284 USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008 OI Shen, Qiang/0000-0002-4287-3403 FU NIH [R01-NS45879]; American Heart Association [EIA 0940104N, 12BGIA 9300047]; Clinical Translational Science Award Pilot Grant; Translational Technology Resource grant [UL1TR000149] FX This work was supported by the NIH (R01-NS45879), the American Heart Association (EIA 0940104N and 12BGIA 9300047), a Clinical Translational Science Award Pilot Grant, and a Translational Technology Resource grant (parent grant UL1TR000149). NR 31 TC 7 Z9 8 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2014 VL 34 IS 1 BP 169 EP 175 DI 10.1038/jcbfm.2013.179 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 282YK UT WOS:000329210700020 PM 24129750 ER PT J AU Weise, G Lorenz, M Posel, C Riegelsberger, UM Storbeck, V Kamprad, M Kranz, A Wagner, DC Boltze, J AF Weise, Gesa Lorenz, Marlene Poesel, Claudia Riegelsberger, Ute Maria Stoerbeck, Veronika Kamprad, Manja Kranz, Alexander Wagner, Daniel-Christoph Boltze, Johannes TI Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE experimental stroke; functional recovery; human umbilical cord blood; spontaneously hypertensive rat AB Systemic human umbilical cord blood (HUCB) mononuclear cell (MNC) transplantation was shown to improve outcome after experimental stroke. However, underlying mechanisms are incompletely understood while the influence of cryopreservation on therapeutic impact is a matter of debate. Here, cryopreserved HUCB MNC was injected intravenously 24 hours after stroke in comorbid rats. Applying strict quality assurance criteria, we could replicate neither improved functional outcome nor lesion size reduction as reported in the previous studies. Astrogliosis and endogenous growth factor expression were also found unaltered. Our results suggest additional research to better understand conditions under which HUCB MNC exert beneficial effects after stroke. C1 [Weise, Gesa; Lorenz, Marlene; Poesel, Claudia; Riegelsberger, Ute Maria; Stoerbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, D-04103 Leipzig, Germany. [Weise, Gesa; Wagner, Daniel-Christoph; Boltze, Johannes] Univ Leipzig, Translat Ctr Regenerat Med, D-04109 Leipzig, Germany. [Kamprad, Manja] Univ Leipzig, Inst Clin Immunol, D-04109 Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boltze, Johannes] Harvard Univ, Sch Med, Boston, MA USA. RP Weise, G (reprint author), Fraunhofer Inst Cell Therapy & Immunol, Perlickstr 1, D-04103 Leipzig, Germany. EM gesa.weise@izi.fraunhofer.de NR 6 TC 0 Z9 0 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2014 VL 34 IS 1 BP 182 EP 184 DI 10.1038/jcbfm.2013.185 PG 3 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 282YK UT WOS:000329210700022 ER PT J AU Hilton, JF Shapiro, GI AF Hilton, John F. Shapiro, Geoffrey I. TI Aurora Kinase Inhibition As an Anticancer Strategy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED SOLID TUMORS; SPINDLE ASSEMBLY CHECKPOINT; B-KINASE; PHASE-I; BARASERTIB AZD1152; CELL FATE; CANCER; MLN8237; PHARMACOKINETICS; APOPTOSIS C1 [Hilton, John F.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hilton, JF (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 28 TC 32 Z9 32 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2014 VL 32 IS 1 BP 57 EP 59 DI 10.1200/JCO.2013.50.7988 PG 3 WC Oncology SC Oncology GA 282QJ UT WOS:000329187000010 PM 24043748 ER PT J AU Giuliano, P Spilimbergo, A Tonon, G AF Giuliano, Paola Spilimbergo, Antonio Tonon, Giovanni TI Genetic distance, transportation costs, and trade(1) SO JOURNAL OF ECONOMIC GEOGRAPHY LA English DT Article DE Transportation costs; genetics; trade; cultural economics; geography; Z10; F10 ID GEOGRAPHY AB Genetic distance, geographic proximity, and economic variables are strongly correlated. Disentangling the effects of these factors is crucial for interpreting these correlations. We show that geographic factors that shaped genetic patterns in the past are also relevant for current transportation costs and could explain the correlation between trading flows and genetic distance. After controlling for geography, the impact of genetic distance on trade disappears. We make our point by constructing a database on geographical barriers, by introducing a novel dataset on transportation costs, and by proposing a new classification of goods according to the ease with which they can be transported. C1 [Giuliano, Paola] Univ Calif Los Angeles, NBER, Los Angeles, CA 90095 USA. [Giuliano, Paola] Univ Calif Los Angeles, CEPR, Los Angeles, CA 90095 USA. [Giuliano, Paola] Univ Calif Los Angeles, IZA, Los Angeles, CA 90095 USA. [Spilimbergo, Antonio] CREaM, CEPR, IMF, Washington, DC USA. [Spilimbergo, Antonio] WDI, Washington, DC USA. [Tonon, Giovanni] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Giuliano, P (reprint author), Univ Calif Los Angeles, Anderson Sch Management, 110 Westwood Plaza,C517 Entrepreneurs Hall, Los Angeles, CA 90095 USA. EM paola.giuliano@anderson.ucla.edu RI Giuliano, Paola/J-3159-2013 NR 26 TC 7 Z9 7 U1 6 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1468-2702 EI 1468-2710 J9 J ECON GEOGR JI J. Econ. Geogr. PD JAN PY 2014 VL 14 IS 1 BP 179 EP 198 DI 10.1093/jeg/lbt019 PG 20 WC Economics; Geography SC Business & Economics; Geography GA 280UY UT WOS:000329057500008 ER PT J AU Howard, ZD Noble, VE Marill, KA Sajed, D Rodrigues, M Bertuzzi, B Liteplo, AS AF Howard, Zoe D. Noble, Vicki E. Marill, Keith A. Sajed, Dana Rodrigues, Marcio Bertuzzi, Bianca Liteplo, Andrew S. TI BEDSIDE ULTRASOUND MAXIMIZES PATIENT SATISFACTION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE bedside ultrasound; emergency ultrasound; patient satisfaction; survey ID EMERGENCY-DEPARTMENT; CARE AB Background: Bedside ultrasound (US) is associated with improved patient satisfaction, perhaps as a consequence of improved time to diagnosis and decreased length of stay (LOS). Objectives: Our study aimed to quantify the association between beside US and patient satisfaction and to assess patient attitudes toward US and perception of their interaction with the clinician performing the examination. Methods: We enrolled a convenience sample of adult patients who received a bedside US. The control group had similar LOS and presenting complaints but did not have a bedside US. Both groups answered survey questions during their emergency department (ED) visit and again by telephone 1 week later. The questionnaire assessed patient perceptions and satisfaction on a 5-point Likert scale. Results: Seventy patients were enrolled over 10 months. The intervention group had significantly higher scores on overall ED satisfaction (4.69 vs. 4.23; mean difference 0.46; 95% confidence interval [CI] 0.17-0.75), diagnostic testing (4.54 vs. 4.09; mean difference 0.46; 95% CI 0.16-0.76), and skills/abilities of the emergency physician (4.77 vs. 4.14; mean difference 0.63; 95% CI 0.29-0.96). A trend to higher scores for the intervention group persisted on follow-up survey. Conclusions: Patients who had a bedside US had statistically significant higher satisfaction scores with overall ED care, diagnostic testing, and with their perception of the emergency physician. Bedside US has the potential not only to expedite care and diagnosis, but also to maximize satisfaction scores and improve the patient-physician relationship, which has increasing relevance to health care organizations and hospitals that rely on satisfaction surveys. (C) 2014 Elsevier Inc. C1 [Howard, Zoe D.; Noble, Vicki E.; Marill, Keith A.; Rodrigues, Marcio; Bertuzzi, Bianca; Liteplo, Andrew S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Sajed, Dana] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA. RP Howard, ZD (reprint author), Stanford Univ, Med Ctr, Div Emergency Med, 300 Pasteur Dr,Always Bldg M121, Stanford, CA 94305 USA. NR 11 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2014 VL 46 IS 1 BP 46 EP 53 DI 10.1016/j.jemermed.2013.05.044 PG 8 WC Emergency Medicine SC Emergency Medicine GA 276JK UT WOS:000328746400015 PM 23942153 ER PT J AU Lobachova, L Brown, DFM Sinclair, J Chang, YC Thielker, KZ Nagurney, JT AF Lobachova, Lana Brown, David F. M. Sinclair, Julia Chang, Yuchaio Thielker, Korie Zink Nagurney, John T. TI PATIENT AND PROVIDER PERCEPTIONS OF WHY PATIENTS SEEK CARE IN EMERGENCY DEPARTMENTS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency department; utilization; overcrowding; health-care-seeking behavior; referral ID REDUCTION; OUTCOMES; VISITS; TRIAGE; IMPACT AB Background: Little is known about why patients choose emergency departments (EDs) to receive care. Objective: Our aim was to measure the distribution and frequency of the stated reasons why patients choose the ED for care and why primary care physicians (PCPs) think their patients utilize the ED. Methods: The authors conducted a survey of patients presenting to an ED with 92,000 annual visits. Appropriate parametric tests were used for univariate and multivariate analysis and results were presented as frequencies with 95% confidence intervals. The authors also performed a cross-sectional survey of PCPs through a web-based survey. Results: Of the 1515 patients approached, 1083 (71%) agreed to participate and 1062 (98%) of them completed the survey. The most common reason patients gave for coming to the ED was their belief that their problem was serious (61%), followed by being referred (35%). In addition, 48% came at the advice of a provider, family member, or friend. By self-report, 354 (33%) patients attempted to reach their PCPs and 306 (86%) of them were successful. Two hundred and seventy-five PCPs were also surveyed. The most frequent reasons PCPs thought their patients came to an ED were that the patient chose to go on their own (80%) and the patients felt that they were too sick to be seen in the PCP's office (80%). Conclusions: The majority of patients stated that the most common reason for seeking care in an ED was that they thought their problem was serious. Almost half sought ED care on the advice of a family member, friend, or health care provider, and a sizable minority were actually referred in by a health care provider. PCPs agree that most patients come to EDs because they believe they are too sick to be seen in their office or become sick after office hours. (C) 2014 Elsevier Inc. C1 [Lobachova, Lana] Harvard Univ, Sch Med, Boston, MA USA. [Lobachova, Lana] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Brown, David F. M.; Thielker, Korie Zink; Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Sinclair, Julia] Brigham & Womans Hosp, Clin Serv, Boston, MA USA. [Chang, Yuchaio] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl, Boston, MA 02114 USA. NR 19 TC 4 Z9 4 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2014 VL 46 IS 1 BP 104 EP 112 DI 10.1016/j.jemermed.2013.04.063 PG 9 WC Emergency Medicine SC Emergency Medicine GA 276JK UT WOS:000328746400025 PM 24063881 ER PT J AU Volonte, A Di Tomaso, T Spinelli, M Todaro, M Sanvito, F Albarello, L Bissolati, M Ghirardelli, L Orsenigo, E Ferrone, S Doglioni, C Stassi, G Dellabona, P Staudacher, C Parmiani, G Maccalli, C AF Volonte, Andrea Di Tomaso, Tiziano Spinelli, Michela Todaro, Matilde Sanvito, Francesca Albarello, Luca Bissolati, Massimiliano Ghirardelli, Luca Orsenigo, Elena Ferrone, Soldano Doglioni, Claudio Stassi, Giorgio Dellabona, Paolo Staudacher, Carlo Parmiani, Giorgio Maccalli, Cristina TI Cancer-Initiating Cells from Colorectal Cancer Patients Escape from T Cell-Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STEM-CELLS; INTERLEUKIN-4; PROLIFERATION; PHENOTYPE; GROWTH; TUMORS; LINES AB Cancer-initiating cells (CICs) that are responsible for tumor initiation, propagation, and resistance to standard therapies have been isolated from human solid tumors, including colorectal cancer (CRC). The aim of this study was to obtain an immunological profile of CRC-derived CICs and to identify CIC-associated target molecules for T cell immunotherapy. We have isolated cells with CIC properties along with their putative non-CIC autologous counterparts from human primary CRC tissues. These CICs have been shown to display "tumor-initiating/stemness" properties, including the expression of CIC-associated markers (e. g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenicity following injection in immunodeficient mice. The immune profile of these cells was assessed by phenotype analysis and by in vitro stimulation of PBMCs with CICs as a source of Ags. CICs, compared with non-CIC counterparts, showed weak immunogenicity. This feature correlated with the expression of high levels of immunomodulatory molecules, such as IL-4, and with CIC-mediated inhibitory activity for anti-tumor T cell responses. CIC-associated IL-4 was found to be responsible for this negative function, which requires cell-to-cell contact with T lymphocytes and which is impaired by blocking IL-4 signaling. In addition, the CRC-associated Ag COA-1 was found to be expressed by CICs and to represent, in an autologous setting, a target molecule for anti-tumor T cells. Our study provides relevant information that may contribute to designing new immunotherapy protocols to target CICs in CRC patients. C1 [Volonte, Andrea; Di Tomaso, Tiziano; Spinelli, Michela; Parmiani, Giorgio; Maccalli, Cristina] San Raffaele Fdn Ctr, Unit Immunobiotherapy Melanoma & Solid Tumors, I-20132 Milan, Italy. [Todaro, Matilde; Stassi, Giorgio] Univ Palermo, Dept Surg & Oncol Sci, I-90128 Palermo, Italy. [Sanvito, Francesca; Albarello, Luca; Doglioni, Claudio] Hosp San Raffaele, Unit Pathol, I-20132 Milan, Italy. [Bissolati, Massimiliano; Ghirardelli, Luca; Orsenigo, Elena; Staudacher, Carlo] Hosp San Raffaele, Dept Oncol, Unit Gastroenterol Surg, I-20132 Milan, Italy. [Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dellabona, Paolo] San Raffaele Fdn Ctr, Expt Immunol Unit, I-20132 Milan, Italy. RP Maccalli, C (reprint author), San Raffaele Fdn Ctr, Unit Immunobiotherapy Melanoma & Solid Tumors, Div Mol Oncol, Via Olgettina 58, I-20132 Milan, Italy. EM maccalli.cristina@hsr.it OI DOGLIONI, Claudio/0000-0002-4969-5216; Dellabona, Paolo/0000-0002-1414-633X; Bissolati, Massimiliano/0000-0002-2032-0138 FU Italian Alliance against Cancer (Rome) FX This work was supported by the Italian Alliance against Cancer (Rome) in the form of a grant to G. Parmiani. NR 33 TC 23 Z9 24 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2014 VL 192 IS 1 BP 523 EP 532 DI 10.4049/jimmunol.1301342 PG 10 WC Immunology SC Immunology GA 279HJ UT WOS:000328950700054 PM 24277698 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI The Influence of Emerging Administrative Scientists An Interview With Dr Maja Djukic SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID REGISTERED NURSES; EDUCATION; QUALITY; SAMPLE; MODEL AB This department highlights emerging nursing leaders and scientists who have demonstrated great promise and findings in advancing innovation and patient care leadership in practice, policy, research, education and theory. This interview profiles Maja Djukic, PhD, RN, assistant professor, New York University College of Nursing. C1 [Adams, Jeffrey M.] Ctr Innovat Care Delivery, Boston, MA USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB4, Boston, MA 02114 USA. EM jadams9@partners.org NR 8 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD JAN PY 2014 VL 44 IS 1 BP 8 EP 9 DI 10.1097/NNA.0000000000000014 PG 2 WC Nursing SC Nursing GA 279CM UT WOS:000328937000005 ER PT J AU Delling, FN Gona, P Larson, MG Lehman, B Manning, WJ Levine, RA Benjamin, EJ Vasan, RS AF Delling, Francesca N. Gona, Philimon Larson, Martin G. Lehman, Birgitta Manning, Warren J. Levine, Robert A. Benjamin, Emelia J. Vasan, Ramachandran S. TI Mild Expression of Mitral Valve Prolapse in the Framingham Offspring: Expanding the Phenotypic Spectrum SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Mitral valve prolapse; Echocardiography ID TERM FOLLOW-UP; NATURAL-HISTORY; AORTIC-ANEURYSM; MARFAN-SYNDROME; VENA CONTRACTA; REGURGITATION; DIAGNOSIS; SEVERITY; LOCUS; RECONSTRUCTION AB Background: Mitral valve (MV) prolapse (MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. Nondiagnostic morphologies have been described in the familial context and may represent early expression of MVP in those genetically predisposed. The aim of this study was to explore the spectrum of MVP abnormalities in the community and compare their clinical and echocardiographic features. Methods: We measured annular diameter MV leaflet displacement, thickness, anterior and posterior leaflet projections onto the annulus, MV leaflet coaptation height (posterior MV leaflet projection/annular diameter), and MR jet height in 296 individuals of the Framingham Offspring Study with MVP (n = 77), the "abnormal anterior coaptation" (AAC) phenotype (n = 11) or "minimal systolic displacement" (MSD) (n = 57), and 151 age-matched and sex-matched referents with no MVP or its nondiagnostic forms. Results: AAC did not meet diagnostic displacement criteria but resembled MVP with regard to annular diameter and leaflet thickness (P > .05 for both). AAC was similar to posterior MVP with regard to posterior leaflet asymmetry and an anteriorly shifted coaptation (P = .91). Compared to patients with MSD and referents, patients with AAC had greater leaflet coaptation height, thickness, and annular diameter (P < .05 for all). MSD shared the posterior leaflet asymmetry with MVP, but the coaptation point was more posterior (coaptation height = 31% vs. 42%, P < .0001), as seen in referents. A higher proportion of patients with MVP had jet height >= 2 mm (mild or greater MR) compared with the other participants (44% vs. 16%, P < .0001). Conclusions: Nondiagnostic morphologies are observed in the community and share the common feature of posterior leaflet asymmetry with MVP. AAC and MSD may thus represent early expressions of MVP. Longitudinal studies are warranted to elucidate the natural history of these phenotypes. C1 [Delling, Francesca N.; Gona, Philimon; Larson, Martin G.; Lehman, Birgitta; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Delling, Francesca N.; Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02215 USA. [Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Larson, Martin G.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Dept Med, Boston, MA USA. RP Delling, FN (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, E-SH-458,330 Brookline Ave, Boston, MA 02215 USA. EM fdelling@bidmc.harvard.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Founders Affiliate American Heart Association Clinical Research Program; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, R01HL080124, RO1HL0107385] FX This work was supported by the Founders Affiliate American Heart Association Clinical Research Program (Dr Delling) and by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), R01HL080124, and RO1HL0107385 (Dr Vasan). NR 39 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2014 VL 27 IS 1 BP 17 EP 23 DI 10.1016/j.echo.2013.09.015 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281PN UT WOS:000329113600005 PM 24206636 ER PT J AU Ajay, AK Kim, TM Ramirez-Gonzalez, V Park, PJ Frank, DA Vaidya, VS AF Ajay, Amrendra Kumar Kim, Tae-Min Ramirez-Gonzalez, Victoria Park, Peter J. Frank, David A. Vaidya, Vishal S. TI A Bioinformatics Approach Identifies Signal Transducer and Activator of Transcription-3 and Checkpoint Kinase 1 as Upstream Regulators of Kidney Injury Molecule-1 after Kidney Injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; TUBULAR INJURY; EMERGING ROLE; CELLS; TIM-1; FIBROSIS; BIOMARKERS; DAMAGE; REPERFUSION; EXPRESSION AB Kidney injury molecule-1 (KIM-1)/T cell Ig and mucin domain-containing protein-1 (TIM-1) is upregulated more than other proteins after AKI, and it is highly expressed in renal damage of various etiologies. In this capacity, KIM-1/TIM-1 acts as a phosphatidylserine receptor on the surface of injured proximal tubular epithelial cells, mediating phagocytosis of apoptotic cells, and it may also act as a costimulatory molecule for immune cells. Despite recognition of KIM-1 as an important therapeutic target for kidney disease, the regulators of KIM-1 transcription in the kidney remain unknown. Using a bioinformatics approach, we identified upstream regulators of KIM-1 after AKI. In response to tubular injury in rat and human kidneys or oxidant stress in human proximal tubular epithelial cells (HPTECs), KIM-1 expression increased significantly in a manner that corresponded temporally and regionally with increased phosphorylation of checkpoint kinase 1 (Chk1) and STAT3. Both ischemic and oxidant stress resulted in a dramatic increase in reactive oxygen species that phosphorylated and activated Chk1, which subsequently bound to STAT3, phosphorylating it at S727. Furthermore, STAT3 bound to the KIM-1 promoter after ischemic and oxidant stress, and pharmacological or genetic induction of STAT3 in HPTECs increased KIM-1 mRNA and protein levels. Conversely, inhibition of STAT3 using siRNAs or dominant negative mutants reduced KIM-1 expression in a kidney cancer cell line (769-P) that expresses high basal levels of KIM-1. These observations highlight Chk1 and STAT3 as critical upstream regulators of KIM-1 expression after AKI and may suggest novel approaches for therapeutic intervention. C1 [Ajay, Amrendra Kumar; Vaidya, Vishal S.] Harvard Inst Med, Dept Med, Div Renal, Boston, MA USA. [Ajay, Amrendra Kumar; Kim, Tae-Min; Park, Peter J.; Frank, David A.; Vaidya, Vishal S.] Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. [Kim, Tae-Min; Park, Peter J.] Harvard Inst Med, Ctr Biomed Informat, Boston, MA USA. [Ramirez-Gonzalez, Victoria] Inst Nacl Ciencias Med Nutr Salvador Zubiran, Dept Nefrol Metab Mineral, Mexico City, DF, Mexico. [Frank, David A.] Dana Farber Canc Res Inst, Dept Med Oncol, Boston, MA USA. [Vaidya, Vishal S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Vaidya, VS (reprint author), Harvard Univ, Brigham & Womens Hosp, Lab Kidney Toxicol & Regenerat, Med Sch,Dept Med,Renal Div,Harvard Inst Med, Rm 510,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vvaidya@partners.org RI Ajay, Amrendra/D-7431-2016; OI Ajay, Amrendra/0000-0003-2790-5726; Ramirez, Victoria/0000-0002-2782-1381 FU National Institutes of Health Outstanding New Environmental Scientist Award [ES017543] FX The laboratory of V.S.V. is supported by National Institutes of Health Outstanding New Environmental Scientist Award ES017543. NR 50 TC 10 Z9 11 U1 0 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2014 VL 25 IS 1 BP 105 EP 118 DI 10.1681/ASN.2013020161 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 282FN UT WOS:000329155800013 PM 24158981 ER PT J AU Wong, SPY Kreuter, W O'Hare, AM AF Wong, Susan P. Y. Kreuter, William O'Hare, Ann M. TI Healthcare Intensity at Initiation of Chronic Dialysis among Older Adults SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; LONG-TERM DIALYSIS; OF-LIFE CARE; ADVANCE CARE; DECISION-MAKING; STARTING DIALYSIS; END; INDEPENDENCE; NEPHROLOGY; SURVIVAL AB Little is known about the circumstances under which older adults initiate chronic dialysis and subsequent outcomes. Using national registry data, we conducted a retrospective analysis of 416,657 Medicare beneficiaries aged 67 years who initiated chronic dialysis between January 1995 and December 2008. Our goal was to define the relationship between health care intensity around the time of dialysis initiation and subsequent survival and patterns of hospitalization, use of intensive procedures (mechanical ventilation, feeding tube placement, and cardiopulmonary resuscitation), and discontinuation of dialysis before death. We found that most patients (64.5%) initiated dialysis in the hospital, including 36.6% who were hospitalized for 2 weeks and 7.4% who underwent one or more intensive procedures. Compared with patients who initiated dialysis in the outpatient setting, those who received the highest intensity of care at dialysis initiation (those hospitalized 2 weeks and receiving at least one intensive procedure) had a shorter median survival (0.7 versus 2.1 years; P<0.001), spent a greater percentage of remaining follow-up time in the hospital (median, 22.9% versus 3.1%; P<0.001), were more likely to undergo subsequent intensive procedures (44.9% versus 26.0%; adjusted hazard ratio, 2.33; 95% confidence interval [CI], 2.27 to 2.39), and were less likely to have discontinued dialysis before death (19.1% versus 26.2%; adjusted odds ratio, 0.68; 95% CI, 0.65 to 0.72). In conclusion, most older adults initiate chronic dialysis in the hospital. Those who have a prolonged hospital stay and receive other forms of life support around the time of dialysis initiation have limited survival and more intensive patterns of subsequent healthcare utilization. C1 [Wong, Susan P. Y.; O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kreuter, William] Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Wong, SPY (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,Box 356521, Seattle, WA 98195 USA. EM spywong@uw.edu FU Veterans Affairs Puget Sound Healthcare System; Centers for Disease Control and Prevention; National Institute on Aging; Veterans Affairs Health Services Research and Development Service FX A.M.O. receives research funding from an interagency agreement between the Veterans Affairs Puget Sound Healthcare System and the Centers for Disease Control and Prevention and from grants from the National Institute on Aging and the Veterans Affairs Health Services Research and Development Service. She also receives royalties from UpToDate. NR 29 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2014 VL 25 IS 1 BP 143 EP 149 DI 10.1681/ASN.2013050491 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 282FN UT WOS:000329155800016 PM 24262795 ER PT J AU Ghani, KR Roghmann, F Sammon, JD Trudeau, V Sukumar, S Rahbar, H Kumar, R Karakiewicz, PI Peabody, JO Menon, M Sun, M Trinh, QD AF Ghani, Khurshid R. Roghmann, Florian Sammon, Jesse D. Trudeau, Vincent Sukumar, Shyam Rahbar, Haider Kumar, Ramesh Karakiewicz, Pierre I. Peabody, James O. Menon, Mani Sun, Maxine Quoc-Dien Trinh TI Emergency Department Visits in the United States for Upper Urinary Tract Stones: Trends in Hospitalization and Charges SO JOURNAL OF UROLOGY LA English DT Article DE urinary tract; urolithiasis; emergencies; hospitalization; fees and charges ID GENDER PREVALENCE; PRACTICE PATTERNS; KIDNEY-STONES; MANAGEMENT; NEPHROLITHIASIS; UROLITHIASIS; OUTCOMES; OBESITY; CALCULI; DISEASE AB Purpose: Using the Nationwide Emergency Department Sample (NEDS) we examined trends in visits, hospitalization and charges for patients with upper urinary tract stones who presented to the emergency department in the United States. Materials and Methods: All visits with a primary diagnosis of kidney calculus (ICD-9-CM code 592.0), ureter calculus (592.1) or urinary calculus unspecified (592.9) were extracted from NEDS between 2006 and 2009. A weighted sample was used to calculate incidence rates. Temporal trends were quantified by the estimated annual percent change. Patient and hospital characteristics associated with hospitalization were evaluated using logistic regression models adjusted for clustering. Results: Between 2006 and 2009 there were 3,635,054 emergency department visits for upper urinary tract stones. The incidence increased from 289 to 306/100,000 individuals. More men visited than women but women showed significant increases in visits (estimated annual percent change 2.85%, p = 0.018). Total monthly emergency department visits ranged from 5.8% in February to 8.4% in August. Overall 12.0% of patients were hospitalized and the hospitalization rate remained stable (estimated annual percent change -1.02%, p = 0.634). Patients were more likely to be hospitalized if they were female, more ill, seen at an urban teaching or low volume hospital, or had Medicaid or Medicare (each p < 0.001). Sepsis was associated with the highest likelihood of hospital admission (OR 69.64, p < 0.001). In 2009 charges for emergency department visits increased to $5 billion (estimated annual percent change 10.06%, p = 0.003). Conclusions: Women showed significant annual increases in emergency department visits for upper urinary tract stones. While emergency department charges increased substantially, hospitalization rates remained stable. Greater use of computerized tomography and medical expulsive therapy could be the reasons for this observation, which warrants further study. C1 [Ghani, Khurshid R.; Sammon, Jesse D.; Sukumar, Shyam; Rahbar, Haider; Kumar, Ramesh; Peabody, James O.; Menon, Mani; Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Div Urol Surg, Boston, MA USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth,Dana Farber Canc Inst, Boston, MA 02115 USA. [Roghmann, Florian; Trudeau, Vincent; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Quebec City, PQ, Canada. [Roghmann, Florian] Ruhr Univ Bochum, Marienhosp, Dept Urol, Herne, Germany. RP Ghani, KR (reprint author), Univ Michigan, Dept Urol, 1500 East Med Ctr Dr,3875 Taubman Ctr, Ann Arbor, MI 48109 USA. EM kghani@med.umich.edu FU Urology Foundation FX Supported by a fellowship from The Urology Foundation (KRG). NR 26 TC 19 Z9 20 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JAN PY 2014 VL 191 IS 1 BP 90 EP 96 DI 10.1016/j.juro.2013.07.098 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 282RY UT WOS:000329191700032 PM 23933053 ER PT J AU Fernandes, TL Fregni, F Weaver, K Pedrinelli, A Camanho, GL Hernandez, AJ AF Fernandes, Tiago Lazzaretti Fregni, Felipe Weaver, Kayleen Pedrinelli, Andre Camanho, Gilberto Luis Hernandez, Arnaldo Jose TI The influence of femoral tunnel position in single-bundle ACL reconstruction on functional outcomes and return to sports SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE Sports medicine; Anterior cruciate ligament/injuries/surgery; Anatomic; Single-bundle; Transtibial; Imaging; Outcome ID ANTERIOR CRUCIATE LIGAMENT; HAMSTRING TENDON AUTOGRAFTS; MUSCLE STRENGTH; GRAFT PLACEMENT; KNEE; PATELLAR; BONE; SEMITENDINOSUS AB The purpose of this study was to radiographically investigate the influence of femoral tunnel placement in ACL reconstruction on early outcomes and return to sports due to anatomic and nonanatomic positioning. A prospective study was conducted from 2008 to 2010, with 86 athletes who underwent ACL reconstruction between anteromedial (AM) footprint and high AM position. Knee functional outcomes (IKDC objective and subjective, Tegner score, and Lysholm scale) return to sports and complications were analyzed at 6- and 12-month follow-up. At follow-up, it was observed that tunnel projection along Blumensaat's line was correlated with functional outcomes on Tegner scale (at 6 and 12 months) and IKDC subjective (at 12 months). There was a significant difference in mean tunnel projection along Blumensaat's line when analyzing return to sports (73 +/- A 1.4 and 79 +/- A 1.7 %, respectively, for projections on return vs. no return to sports, p = 0.02) and complications (73 +/- A 1.3 vs. 78 +/- A 1.6 %, respectively, for projections on no complications vs. complications, p = 0.03). No differences were stated on coronal view. These correlations between tunnel positioning on functional outcomes could not be explained by demographic or baseline characteristics. The clinical relevance of this study is that tunnel positioning along AM footprint and high AM position represented by tunnel projection along Blumensaat's line is associated with early return to sports on previous Tegner level and better functional outcome in athletes. III. C1 [Fernandes, Tiago Lazzaretti; Pedrinelli, Andre; Camanho, Gilberto Luis; Hernandez, Arnaldo Jose] Univ Sao Paulo, Sch Med, Hosp Clin, Inst Orthoped & Traumatol, BR-05403010 Sao Paulo, Brazil. [Fernandes, Tiago Lazzaretti; Pedrinelli, Andre; Camanho, Gilberto Luis; Hernandez, Arnaldo Jose] FIFA Med Ctr Excellence, Sao Paulo, Brazil. [Fregni, Felipe; Weaver, Kayleen] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, Boston, MA USA. [Fregni, Felipe; Weaver, Kayleen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fernandes, TL (reprint author), Univ Sao Paulo, Sch Med, Hosp Clin, Inst Orthoped & Traumatol, 333 Dr Ovidio Pires Campos, BR-05403010 Sao Paulo, Brazil. EM tiago.lazzaretti@usp.br NR 35 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 EI 1433-7347 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD JAN PY 2014 VL 22 IS 1 BP 97 EP 103 DI 10.1007/s00167-012-2288-8 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 283JC UT WOS:000329241300013 PM 23132410 ER PT J AU Messner, A Teng, M Shimahara, E Abaza, M Franzese, C Goebel, J Gray, S Joe, S Ruckenstein, M Takashima, M Wax, M Zacharek, M AF Messner, Anna Teng, Marita Shimahara, Erika Abaza, Mona Franzese, Christine Goebel, Joel Gray, Stacey Joe, Stephanie Ruckenstein, Michael Takashima, Mas Wax, Mark Zacharek, Mark TI A Case for the Standardized Letter of Recommendation in Otolaryngology Residency Selection SO LARYNGOSCOPE LA English DT Editorial Material C1 [Messner, Anna; Shimahara, Erika] Stanford Univ, Dept Otolaryngol Head & Neck Surg, Palo Alto, CA 94304 USA. [Teng, Marita] Icahn Sch Med Mt Sinai, Dept Otolaryngol, New York, NY USA. [Abaza, Mona] Univ Colorado, Dept Otolaryngol Head & Neck Surg, Denver, CO 80202 USA. [Franzese, Christine] Eastern Virginia Med Sch, Dept Otolaryngol Head & Neck Surg, Norfolk, VA 23501 USA. [Goebel, Joel] Washington Univ, Dept Otolaryngol Head & Neck Surg, St Louis, MO USA. [Gray, Stacey] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Joe, Stephanie] Univ Illinois, Dept Otolaryngol Head & Neck Surg, Chicago, IL USA. [Ruckenstein, Michael] Univ Penn, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Takashima, Mas] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. [Wax, Mark] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Zacharek, Mark] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. RP Messner, A (reprint author), Stanford Univ, Dept Otolaryngol Head & Neck Surg, Palo Alto, CA 94304 USA. NR 2 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2014 VL 124 IS 1 BP 2 EP 3 DI 10.1002/lary.24431 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 276HB UT WOS:000328738800003 PM 24155034 ER PT J AU Wu, AW Ting, JY Platt, MP Tierney, HT Metson, R AF Wu, Arthur W. Ting, Jonathan Y. Platt, Michael P. Tierney, Hien T. Metson, Ralph TI Factors Affecting Time to Revision Sinus Surgery for Nasal Polyps: A 25-Year Experience SO LARYNGOSCOPE LA English DT Article DE Nasal polyps; chronic rhinosinusitis; endoscopic sinus surgery; revision sinus surgery ID MIDDLE TURBINATE RESECTION; CHRONIC RHINOSINUSITIS; STAGING SYSTEMS; OUTCOMES; SMOKING; RATES AB Objectives/HypothesisSurgical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) is often followed by polyp regrowth with return of symptoms. The purpose of this study is to identify clinical factors that influence the time interval to revision sinus surgery in patients with nasal polyps. Study DesignRetrospective cohort study. MethodsRecords of 299 individuals who underwent two or more surgeries for the diagnosis of nasal polyps by the senior author (RM) from 1987 through 2011 were reviewed. The time between surgical interventions were compared to patient demographics, comorbidities, endoscopic examination, computed tomography (CT) stage, extent of surgery, and pathologic findings. ResultsThe mean time interval between polyp surgeries was 4.873.61 years (range 0.7-18.6 years). The median time to revision surgery was shorter in patients who smoked compared to nonsmokers (2.82 vs. 4.31 years, respectively, P=.022) and longer in patients who underwent middle turbinate resection rather than preservation (4.56 vs. 3.93 years, respectively, P=.048). Kaplan-Meier survival analysis confirmed these findings, but the beneficial effect of turbinectomy appeared to dissipate by 8 years. Neither a history of asthma nor advanced CT stage influenced the time to revision surgery. ConclusionThe time course between sinus surgeries in patients with regrowth of nasal polyps appears to be affected by certain modifiable extrinsic factors, including smoking on the part of the patient and operative technique on the part of the surgeon. The performance of middle turbinate resection during sinus surgery appears to extend the time interval until a revision procedure is required. C1 [Wu, Arthur W.; Ting, Jonathan Y.; Metson, Ralph] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Dept Otol & Laryngol, Boston, MA USA. [Platt, Michael P.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. EM Ralph_Metson@meei.harvard.edu NR 15 TC 18 Z9 19 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2014 VL 124 IS 1 BP 29 EP 33 DI 10.1002/lary.24213 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 276HB UT WOS:000328738800013 PM 23712679 ER PT J AU Sethi, R Kozin, E Remenschneider, A Meier, J VanderLaan, P Faquin, W Deschler, D Frankenthaler, R AF Sethi, Roshan Kozin, Elliott Remenschneider, Aaron Meier, Josh VanderLaan, Paul Faquin, William Deschler, Daniel Frankenthaler, Robert TI Mammary Analogue Secretory Carcinoma: Update on a New Diagnosis of Salivary Gland Malignancy SO LARYNGOSCOPE LA English DT Review DE Salivary gland carcinoma; mammary analogue secretory carcinoma; head and neck surgery; parotid malignancy ID ETV6-NTRK3 GENE FUSION; ACINIC CELL-CARCINOMA; MUCOEPIDERMOID CARCINOMA; CONGENITAL FIBROSARCOMA; PAROTID-GLAND; BREAST; TUMORS; RADIOTHERAPY; EXPRESSION; FEATURES AB Objectives/HypothesisTo review the known histopathologic findings and clinical behavior of mammary analogue secretory carcinoma (MASC). Data SourcesPubMed. Review MethodsLiterature search using the terms Mammary analogue secretory carcinoma, Mammary analog secretory carcinoma, and MASC to identify all relevant publications. ResultsMASC is an unusual and rare malignant salivary gland tumor first described in 2010. It shares histologic, immunohistochemical, and genetic features with secretory carcinoma of the breast. The clinical behavior of MASC ranges from slowly growing tumors that infrequently recur after surgical resection to aggressive tumors that cause widespread metastasis and death. Many cases of MASC were discovered in archived cases previously classified as acinic cell carcinoma, mucoepidermoid carcinoma, and adenocarcinoma not otherwise specified. ConclusionMASC is a newly recognized variant of salivary gland malignancy. Further research is needed to better delineate its overall prevalence and to define an appropriate treatment algorithm for this new clinical entity. C1 [Sethi, Roshan] Harvard Univ, Sch Med, Boston, MA USA. [Kozin, Elliott; Remenschneider, Aaron; Meier, Josh; Deschler, Daniel] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [VanderLaan, Paul; Frankenthaler, Robert] Beth Israel Deaconess Med Ctr, Div Otolaryngol, Boston, MA USA. [VanderLaan, Paul; Frankenthaler, Robert] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. [Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kozin, E (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Elliott_kozin@meei.harvard.edu RI Kozin, Elliott/J-1225-2014; OI Kozin, Elliott/0000-0002-0305-0682; VanderLaan, Paul/0000-0002-7234-5652 FU Doris Duke Charitable Foundation FX This work was supported by a grant from the Doris Duke Charitable Foundation to Harvard Medical School to fund Clinical Research Fellow Roshan Sethi. The authors have no other funding, financial relationships, or conflicts of interest to disclose. From the Harvard Medical School (R. S.); the Department of Otology and Laryngology (E. K., A. R., J.M., D. D.), Massachusetts Eye and Ear Infirmary, Harvard Medical School; the Division of Otolaryngology (R. F., P.VL.), Beth Israel Medical Center; and the Department of Pathology, Beth Israel Medical Center, Boston, Massachusetts, U. S. A, Department of Pathology (W. F.), Massachusetts General Hospital, Boston, Massachusetts, U.S.A NR 34 TC 20 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2014 VL 124 IS 1 BP 188 EP 195 DI 10.1002/lary.24254 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 276HB UT WOS:000328738800039 PM 23775296 ER PT J AU Hohman, MH Bhama, PK Hadlock, TA AF Hohman, Marc H. Bhama, Prabhat K. Hadlock, Tessa A. TI Epidemiology of Iatrogenic Facial Nerve Injury: A Decade of Experience SO LARYNGOSCOPE LA English DT Article DE Facial nerve; facial paralysis; iatrogenic injury ID TEMPOROMANDIBULAR-JOINT; SURGERY; SYSTEM; RHYTIDECTOMY AB Objectives/HypothesisTo determine the procedure-specific incidence, risk factors, and injury patterns in patients with iatrogenic facial nerve injury as seen at a tertiary care facial nerve center. Study DesignRetrospective chart review. MethodsFacial Nerve Center patient records from 2002 to 2012 were reviewed for cases of iatrogenic facial nerve injury. These were analyzed by type of inciting procedure, injury location, patient demographics, and referral pattern. ResultsOut of 1,810 patient records, 102 were identified that involved iatrogenic facial nerve injury. Oral and maxillofacial surgical procedures accounted for 40% of injuries, resections of head and neck lesions 25%, otologic procedures 17%, cosmetic procedures 11%, and other procedures 7%. The most common operation resulting in facial nerve injury was temporomandibular joint replacement. The most frequent pattern of injury was total hemifacial weakness. ConclusionsIatrogenic facial nerve injury occurs most commonly in temporomandibular joint replacement, mastoidectomy, and parotidectomy. Direct visualization of the nerve may decrease the incidence of injury, and early referral for facial nerve exploration may result in improved outcomes. C1 [Hohman, Marc H.; Bhama, Prabhat K.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Hohman, Marc H.; Bhama, Prabhat K.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Boston, MA 02114 USA. RP Hohman, MH (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM marc_hohman@meei.harvard.edu NR 15 TC 6 Z9 7 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2014 VL 124 IS 1 BP 260 EP 265 DI 10.1002/lary.24117 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 276HB UT WOS:000328738800050 PM 23606475 ER PT J AU Pittman, CB Davis, LA Zeringue, AL Caplan, L Wehmeier, KR Scherrer, JF Xian, H Cunningham, FE McDonald, JR Arnold, A Eisen, SA AF Pittman, Cory B. Davis, Lisa A. Zeringue, Angelique L. Caplan, Liron Wehmeier, Kent R. Scherrer, Jeffrey F. Xian, Hong Cunningham, Francesca E. McDonald, Jay R. Arnold, Alexis Eisen, Seth A. TI Myocardial Infarction Risk Among Patients With Fractures Receiving Bisphosphonates SO MAYO CLINIC PROCEEDINGS LA English DT Article ID POSITIVE PREDICTIVE-VALUE; CORONARY-ARTERY; CARDIOVASCULAR-DISEASE; ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE EHDP; AORTIC CALCIFICATION; ATRIAL-FIBRILLATION; BONE-DENSITY; OSTEOPOROSIS; PREVALENCE; DIAGNOSIS AB Objective: To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). Patients and Methods: A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. Results: After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. Conclusion: Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required. (C) 2014 Mayo Foundation for Medical Education and Research C1 [Pittman, Cory B.] Mercy Arthrit & Osteoporosis Ctr, Urbandale, IA 50322 USA. [Davis, Lisa A.] Denver Hlth & Hosp Author, Denver, CO USA. [Davis, Lisa A.; Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Davis, Lisa A.; Caplan, Liron] Univ Colorado, Sch Med, Aurora, CO USA. [Zeringue, Angelique L.; McDonald, Jay R.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Scherrer, Jeffrey F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Wehmeier, Kent R.; Arnold, Alexis] Univ Florida, Coll Med Jacksonville, Dept Med, Div Endocrinol Diabet & Metab, Jacksonville, FL USA. [Xian, Hong] St Louis Univ, Coll Publ Hlth & Social Justice, Dept Biostat, St Louis, MO 63103 USA. [Cunningham, Francesca E.] Vet Affairs Pharm Benefits Management, Hines, IL USA. [Arnold, Alexis] St Olaf Coll, Northfield, MN 55057 USA. [Eisen, Seth A.] Vet Affairs Hlth Serv Res & Dev, Washington, DC USA. RP Pittman, CB (reprint author), Mercy Arthrit & Osteoporosis Ctr, 8421 Plum Dr, Urbandale, IA 50322 USA. EM cpittman@mercydesmoines.org FU National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIH/NIAMS T32 5T32 AR007279, NIH/NIAMS T32 AR007534-24]; National Institutes of Health Loan Repayment Award; Rheumatology Research Foundation Rheumatology Scientist Development Award; Denver Health and Hospital Authority; University of Colorado; Department of Veterans Affairs Health Services Research & Development Career Development Award [CDA 07-221] FX This work was supported in part by National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases grants NIH/NIAMS T32 5T32 AR007279 (C. B. P.) and NIH/NIAMS T32 AR007534-24 (L. A. D.); a National Institutes of Health Loan Repayment Award, the Rheumatology Research Foundation Rheumatology Scientist Development Award, the Denver Health and Hospital Authority, and the University of Colorado (L. A. D.); and Department of Veterans Affairs Health Services Research & Development Career Development Award CDA 07-221 (L.C.). NR 50 TC 6 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2014 VL 89 IS 1 BP 43 EP 51 DI 10.1016/j.mayocp.2013.08.021 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 282IE UT WOS:000329163600011 PM 24388021 ER PT J AU Corrales-Medina, VF Taljaard, M Fine, MJ Dwivedi, G Perry, JJ Musher, DM Chirinos, JA AF Corrales-Medina, Vicente F. Taljaard, Monica Fine, Michael J. Dwivedi, Girish Perry, Jeffrey J. Musher, Daniel M. Chirinos, Julio A. TI Risk Stratification for Cardiac Complications in Patients Hospitalized for Community-Acquired Pneumonia SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SEVERITY INDEX; ADULTS; VALIDATION; MORTALITY; BURDEN; MODELS; SYSTEM AB Objective: To derive and validate a clinical rule that stratifies the risk of cardiac complications in patients hospitalized for community-acquired pneumonia (CAP) and compare its performance to the pneumonia severity index (PSI) score. Patients and Methods: Two cohorts of patients hospitalized for CAP were selected for the study. We used regression techniques in the derivation cohort (1343 patients enrolled in the Pneumonia Patient Outcomes Research Team study between October 1991 and March 1994) to generate a prediction rule that we validated in the validation cohort (608 patients enrolled in the Dissemination of Guidelines for Length of Stay study between February 1998 and March 1999). Discrimination and reclassification analyses compared its performance against the PSI score. Results: A prediction model for cardiac complications in the derivation cohort included age, 3 preexisting conditions, 2 vital signs, and 7 common laboratory or radiographic parameters. Discrimination (C statistic, 0.81; 95% CI, 0.78-0.84) and calibration (Hosmer-Lemeshow goodness-of-fit test, chi(2) = 13.0; P = .11) were good. We derived a point score system from this model that when applied to the validation cohort also had good discrimination (C statistic, 0.78; 95% CI, 0.74-0.83) and calibration (Hosmer-Lemeshow, chi(2) = 9.0; P = .34). On the basis of this score, we defined 4 categories of incremental risk of cardiac complications. The incidence of cardiac complications across risk categories increased linearly (from lowest to highest) in both the derivation (3.0%, 17.8%, 35.2%, and 72.2%) and validation (5.0%, 8.2%, 28.3%, and 48.9%) cohorts (Cochran-Armitage linear trend test, P<.01). The new score outperformed the PSI score in predicting cardiac complications in the validation cohort (C statistic, 0.78 vs 0.74; P = .03; proportion of patients correctly reclassified by the new score, 44%). Conclusion: We derived and validated a clinical rule that accurately stratifies the risk of cardiac complications in patients hospitalized for CAP. (C) 2014 Mayo Foundation for Medical Education and Research C1 [Corrales-Medina, Vicente F.; Dwivedi, Girish] Univ Ottawa, Dept Med, Ottawa Hosp Res Inst, Ottawa, ON K1N 6N5, Canada. [Taljaard, Monica] Univ Ottawa, Ottawa Hosp Res Inst, Dept Epidemiol & Community Med, Ottawa, ON K1N 6N5, Canada. [Perry, Jeffrey J.] Univ Ottawa, Ottawa Hosp Res Inst, Dept Emergency Med, Ottawa, ON K1N 6N5, Canada. [Dwivedi, Girish] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Musher, Daniel M.] Michael E DeBakey VA Med Ctr, Med Care Line Infect Dis Sect, Houston, TX USA. [Chirinos, Julio A.] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Corrales-Medina, VF (reprint author), Ottawa Hosp, Dept Med, ASB 2-003,1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. EM vcorrales@toh.on.ca OI Corrales-Medina, Vicente/0000-0002-9691-491X; Perry, Jeffrey/0000-0003-2134-9597 FU Agency for Healthcare Research and Quality, Rockville, MD; Department of Medicine of the the Ottawa Hospital, Ottawa, Ontario, Canada FX The Pneumonia Patient Outcomes Research Team (PORT) study was funded by the Agency for Healthcare Research and Quality, Rockville, MD. Dr Corrales-Medina is supported by a Research Priority Grant from the Department of Medicine of the the Ottawa Hospital, Ottawa, Ontario, Canada. NR 25 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2014 VL 89 IS 1 BP 60 EP 68 DI 10.1016/j.mayocp.2013.09.015 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 282IE UT WOS:000329163600013 PM 24388023 ER PT J AU McCarthy, JT Hocum, CL Albright, RC Rogers, J Gallaher, EJ Steensma, DP Gudgell, SF Bergstralh, EJ Dillon, JC Hickson, LJ Williams, AW Dingli, D AF McCarthy, James T. Hocum, Craig L. Albright, Robert C. Rogers, James Gallaher, Edward J. Steensma, David P. Gudgell, Stephen F. Bergstralh, Eric. J. Dillon, John C. Hickson, LaTonya J. Williams, Amy W. Dingli, David TI Biomedical System Dynamics to Improve Anemia Control With Darbepoetin Alfa in Long-Term Hemodialysis Patients SO MAYO CLINIC PROCEEDINGS LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CHRONIC KIDNEY-DISEASE; HEMOGLOBIN LEVEL VARIABILITY; DIALYSIS PATIENTS; EPOETIN-ALPHA; MORTALITY; TRIAL; NORMALIZATION; ASSOCIATIONS; HEMATOCRIT AB Objective: To determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population. Patients and Methods: A model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities. All prevalent hemodialysis patients seen from January 1, 2007, through December 31, 2010 (300-342 patients per month), were included with darbepoetin as the ESA. The primary outcome was the percentage of patients who attained the desired hemoglobin level. Secondary outcome measures included the percentage of patients with hemoglobin values above the desired range and mean dose of darbepoetin used. Results: The 3 treatment periods were (1) standard ESA protocol in 2007, (2) transition to the MCAMS (2008 to June 2009), and (3) stability period with the MCAMS used in all hemodialysis facilities (2009 to 2010). In the first 6 months of 2007, 69% of patients were in the desired range and 26% were above the range. In comparison, during the first 5 months of 2010, 83% were in and 6% were above the range (P<.001). The mean monthly darbepoetin dose per patient decreased from 304 mg in 2007 to 173 mg by the second half of 2009 (P<.001). Conclusion: With the introduction of the MCAMS, more patients had hemoglobin levels in the desired range and fewer patients exceeded the target range, with a concomitant 40% reduction in darbepoetin use. (C) 2014 Mayo Foundation for Medical Education and Research C1 [McCarthy, James T.; Hocum, Craig L.; Albright, Robert C.; Gudgell, Stephen F.; Dillon, John C.; Hickson, LaTonya J.; Williams, Amy W.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA. [Gallaher, Edward J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Dingli, David] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Rogers, James; Bergstralh, Eric. J.] Adv Management Grp LLC, Rochester, MN USA. [Steensma, David P.] Dana Farber Brigham & Womens Canc Ctr, Div Hematol Oncol, Boston, MA USA. RP McCarthy, JT (reprint author), Mayo Clin, Div Nephrol & Hypertens, 200 1st St SW, Rochester, MN 55905 USA. EM mccarthy.james@mayo.edu OI Steensma, David/0000-0001-5130-9284 FU Mayo Clinic Division of Nephrology and Hypertension; Minnesota Partnership for Biotechnology and Medical Genomics; Mayo Clinic FX The statistical analysis was funded by the Mayo Clinic Division of Nephrology and Hypertension. No extramural funds or grants were used to fund this analysis. Dr Dingli acknowledges support from the Minnesota Partnership for Biotechnology and Medical Genomics and Mayo Clinic. NR 35 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2014 VL 89 IS 1 BP 87 EP 94 DI 10.1016/j.mayocp.2013.10.022 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 282IE UT WOS:000329163600016 PM 24388026 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI The 1964 "Doctors Mayo" Commemorative Postage Stamp SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. OI Steensma, David/0000-0001-5130-9284 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2014 VL 89 IS 1 BP E1 EP E2 DI 10.1016/j.mayocp.2013.10.031 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 282IE UT WOS:000329163600001 PM 24388034 ER PT J AU Nyame, TT Holzer, PW Helm, DL Maman, DY Winograd, JM Cetrulo, CL AF Nyame, Theodore T. Holzer, Paul W. Helm, Douglas L. Maman, Daniel Y. Winograd, Jonathan M. Cetrulo, Curtis L., Jr. TI SPLIT RECTUS ABDOMINIS MYOCUTANEOUS DOUBLE FREE FLAP FOR EXTREMITY RECONSTRUCTION SO MICROSURGERY LA English DT Article ID GRACILIS MUSCLE; FRACTURES AB A Mathes and Nahai type III muscle, such as the rectus abdominis muscle, can be utilized to cover two separate wounds simultaneously utilizing its dual blood supply thereby minimizing donor site morbidity and operative time. We report a case for treatment of bilateral Gustillo type IIIB lower extremity injuries treated with a single rectus abdominis muscle split into two free flaps, with one based on the deep inferior epigastric vessels and one on the superior epigastric vessels to cover the contralateral wound. In our patient, both lower extremity wounds were covered with muscle flaps from the same donor site in a single operation, salvaging both limbs with progression to unassisted ambulatory status. We show in this case report that the utilization of the vascular anatomy of the rectus muscle allows for division of the flap into two flaps, permitting preservation of the contralateral abdominal wall integrity and coverage of two wounds with a single muscle. (c) 2013 Wiley Periodicals, Inc. C1 [Nyame, Theodore T.; Holzer, Paul W.; Helm, Douglas L.; Maman, Daniel Y.; Winograd, Jonathan M.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Cetrulo, CL (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St WAC 435, Boston, MA 02114 USA. EM ccetrulo@partners.org NR 13 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0738-1085 EI 1098-2752 J9 MICROSURG JI Microsurgery PD JAN PY 2014 VL 34 IS 1 BP 54 EP 57 DI 10.1002/micr.22160 PG 4 WC Surgery SC Surgery GA 278AS UT WOS:000328861000011 PM 24123062 ER PT J AU Pinto, A Nose, V Rojas, C Fan, YS Gomez-Fernandez, C AF Pinto, Andre Nose, Vania Rojas, Claudia Fan, Yao-Shan Gomez-Fernandez, Carmen TI Searching for mammary analog secretory carcinoma of salivary gland among its mimics SO MODERN PATHOLOGY LA English DT Article DE acinic cell carcinoma; ETV6-NTRK3; FISH; immunohistochemistry; mammary analog secretory carcinoma; salivary gland tumors ID ETV6-NTRK3 GENE FUSION; PAROTID-GLAND; FIBROSARCOMA; ENTITY; BREAST AB Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies. C1 [Pinto, Andre; Rojas, Claudia; Fan, Yao-Shan; Gomez-Fernandez, Carmen] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Gomez-Fernandez, C (reprint author), Univ Miami, Miller Sch Med, Dept Pathol, 1400 NW 12 Ave,Room 4076, Miami, FL 33136 USA. EM CGomez3@med.miami.edu NR 23 TC 17 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2014 VL 27 IS 1 BP 30 EP 37 DI 10.1038/modpathol.2013.84 PG 8 WC Pathology SC Pathology GA 282WW UT WOS:000329206200003 PM 23807775 ER PT J AU Kerr, SE Schnabel, CA Sullivan, PS Zhang, Y Huang, VJ Erlander, MG Brachtel, EF Dry, SM AF Kerr, Sarah E. Schnabel, Catherine A. Sullivan, Peggy S. Zhang, Yi Huang, Vivian J. Erlander, Mark G. Brachtel, Elena F. Dry, Sarah M. TI A 92-gene cancer classifier predicts the site of origin for neuroendocrine tumors SO MODERN PATHOLOGY LA English DT Article DE carcinoid; classification; expression; molecular; neuroendocrine ID NANETS CONSENSUS GUIDELINES; PULMONARY CARCINOID-TUMORS; TRANSCRIPTION FACTOR-I; MERKEL CELL-CARCINOMA; PANCREATIC ENDOCRINE; GENE-EXPRESSION; LYMPHOCYTIC-LEUKEMIA; PAX8 EXPRESSION; UNKNOWN PRIMARY; LOW-GRADE AB A diagnosis of neuroendocrine carcinoma is often morphologically straight-forward; however, the tumor site of origin may remain elusive in a metastatic presentation. Neuroendocrine tumor subtyping has important implications for staging and patient management. In this study, the novel use and performance of a 92-gene molecular cancer classifier for determination of the site of tumor origin are described in a series of 75 neuroendocrine tumors (44 metastatic, 31 primary; gastrointestinal (n = 12), pulmonary (n = 22), Merkel cell (n = 10), pancreatic (n = 10), pheochromocytoma (n = 10), and medullary thyroid carcinoma (n = 11)). Formalin-fixed, paraffin-embedded samples passing multicenter pathologist adjudication were blinded and tested by a 92-gene molecular assay that predicts tumor type/subtype based upon relative quantitative PCR expression measurements for 87 tumor-related and 5 reference genes. The 92-gene assay demonstrated 99% (74/75; 95% confidence interval (CI) 0.93-0.99) accuracy for classification of neuroendocrine carcinomas and correctly subtyped the tumor site of origin in 95% (71/75; 95% CI 0.87-0.98) of cases. Analysis of gene expression subsignatures within the 92-gene assay panel showed 4 genes with promising discriminatory value for tumor typing and 15 genes for tumor subtyping. The 92-gene classifier demonstrated excellent accuracy for classifying and determining the site of origin in tumors with neuroendocrine differentiation. These results show promise for use of this test to aid in classifying neuroendocrine tumors of indeterminate primary site, particularly in the metastatic setting. C1 [Kerr, Sarah E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Schnabel, Catherine A.; Zhang, Yi; Huang, Vivian J.; Erlander, Mark G.] bioTheranost Inc, San Diego, CA USA. [Sullivan, Peggy S.; Dry, Sarah M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Brachtel, Elena F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dry, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 13-145 CHS, Los Angeles, CA 90095 USA. EM sdry@mednet.ucla.edu FU bioTheranostics FX CAS, YZ, VH, and ME are employees at bioTheranostics and have ownership interest (including patents) for bioTheranostics. PSS, SMD, and EFB have commercial research funding for bioTheranostics. NR 83 TC 12 Z9 12 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2014 VL 27 IS 1 BP 44 EP 54 DI 10.1038/modpathol.2013.105 PG 11 WC Pathology SC Pathology GA 282WW UT WOS:000329206200005 PM 23846576 ER PT J AU Chen, Y Chauhan, SK Lee, HS Saban, DR Dana, R AF Chen, Y. Chauhan, S. K. Lee, H. Soo Saban, D. R. Dana, R. TI Chronic dry eye disease is principally mediated by effector memory Th17 cells SO MUCOSAL IMMUNOLOGY LA English DT Article ID T-CELLS; DESICCATING STRESS; LACRIMAL KERATOCONJUNCTIVITIS; INTERLEUKIN-17; PREVALENCE; SJOGRENS; HEALTH AB Recent experimental and clinical data suggest that there is a link between dry eye disease (DED) and T-cell-mediated immunity. However, whether these immune responses are a consequence or cause of ocular surface inflammation remains to be determined. Thus far, only models of acute DED have been used to derive experimental data. This is in contrast to clinical DED which usually presents as a chronic disease. In the present study, using a murine model of chronic DED, it was established that the chronic phase of the disease is accompanied by T helper type 17 (Th17) responses at the ocular surface and that a significant memory T-cell population can be recovered from chronic DED. This memory response is predominantly mediated by Th17 cells. Moreover, adoptive transfer of this memory T-cell population was shown to induce more severe and rapidly progressing DED than did the adoptive transfer of its effector or naive counterparts. Not only do these results clearly demonstrate that effector memory Th17 cells are primarily responsible for maintaining the chronic and relapsing course of DED, but they also highlight a potentially novel therapeutic strategy for targeting memory immune responses in patients with DED. C1 [Chen, Y.; Chauhan, S. K.; Lee, H. Soo; Saban, D. R.; Dana, R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. RP Dana, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. EM reza.dana@schepens.harvard.edu FU NIH [EY20889] FX We thank Dr William Stevenson and Gale Unger, Schepens Eye Research Institute, Boston, MA for critical reading of this manuscript, and Dr SangMok Lee, Schepens Eye Research Institute, Boston, MA for quantitative analysis of corneal lymphatic vessels. This work was supported by NIH grant EY20889. NR 35 TC 11 Z9 13 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2014 VL 7 IS 1 BP 38 EP 45 DI 10.1038/mi.2013.20 PG 8 WC Immunology SC Immunology GA 278LX UT WOS:000328892900005 PM 23571503 ER PT J AU Kim, DG Lee, JY Kwon, NH Fang, PF Zhang, Q Wang, J Young, NL Guo, M Cho, HY Mushtaq, AU Jeon, YH Choi, JW Han, JM Kang, HW Joo, JE Hur, Y Kang, W Yang, H Nam, DH Lee, MS Lee, JW Kim, ES Moon, A Kim, K Kim, D Kang, EJ Moon, Y Rhee, KH Han, BW Yang, JS Han, G Yang, WS Lee, C Wang, MW Kim, S AF Kim, Dae Gyu Lee, Jin Young Kwon, Nam Hoon Fang, Pengfei Zhang, Qian Wang, Jing Young, Nicolas L. Guo, Min Cho, Hye Young Mushtaq, Ameeq Ul Jeon, Young Ho Choi, Jin Woo Han, Jung Min Kang, Ho Woong Joo, Jae Eun Hur, Youn Kang, Wonyoung Yang, Heekyoung Nam, Do-Hyun Lee, Mi-Sook Lee, Jung Weon Kim, Eun-Sook Moon, Aree Kim, Kibom Kim, Doyeun Kang, Eun Joo Moon, Youngji Rhee, Kyung Hee Han, Byung Woo Yang, Jee Sun Han, Gyoonhee Yang, Won Suk Lee, Cheolju Wang, Ming-Wei Kim, Sunghoon TI Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction SO NATURE CHEMICAL BIOLOGY LA English DT Article ID ION-CYCLOTRON RESONANCE; MASS-SPECTROMETRY; SCATTERING SAXS; GENE-EXPRESSION; CELL INVASION; SYSTEM; CANCER; METASTASIS; CARCINOMA; PROTEINS AB Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS. C1 [Kim, Dae Gyu; Lee, Jin Young; Kwon, Nam Hoon; Han, Jung Min; Kim, Kibom; Kim, Doyeun; Kang, Eun Joo; Moon, Youngji; Yang, Won Suk; Kim, Sunghoon] Seoul Natl Univ, Med Bioconvergence Res Ctr, Seoul, South Korea. [Kim, Dae Gyu; Lee, Jin Young; Kwon, Nam Hoon; Han, Jung Min; Lee, Mi-Sook; Lee, Jung Weon; Kim, Kibom; Kim, Doyeun; Rhee, Kyung Hee; Han, Byung Woo; Yang, Won Suk; Kim, Sunghoon] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul, South Korea. [Fang, Pengfei; Wang, Jing; Guo, Min] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Zhang, Qian] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. [Young, Nicolas L.] Florida State Univ, Ion Cyclotron Resonance Program, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. [Cho, Hye Young; Mushtaq, Ameeq Ul; Jeon, Young Ho] Korea Univ, Coll Pharm, Sejong, South Korea. [Choi, Jin Woo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Kang, Ho Woong; Joo, Jae Eun; Hur, Youn] Yuhan Res Inst, Yongin, South Korea. [Kang, Wonyoung; Yang, Heekyoung; Nam, Do-Hyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurosurg, Seoul, South Korea. [Kim, Eun-Sook; Moon, Aree] Duksung Womens Univ, Coll Pharm, Seoul, South Korea. [Han, Gyoonhee] Yonsei Univ, Translat Res Ctr Prot Funct Control, Dept Biotechnol, Seoul 120749, South Korea. [Lee, Cheolju] Korea Inst Sci & Technol, BRI, Seoul, South Korea. [Wang, Ming-Wei] Natl Ctr Drug Screening, Shanghai, Peoples R China. [Kim, Sunghoon] Seoul Natl Univ, World Class Univ, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea. RP Kim, DG (reprint author), Seoul Natl Univ, Med Bioconvergence Res Ctr, Seoul, South Korea. EM sungkim@snu.ac.kr RI Lee, Jung Weon/F-9149-2012; Fang, Pengfei/O-3696-2015; OI Fang, Pengfei/0000-0002-3448-5494; Young, Nicolas/0000-0002-3323-2815 FU Global Frontier Project [M1AXA002-20100029785, NRF-M1AXA002-2010-0029765, NRF-2012M3A6A4054271, NRF-2012-054237]; World Class University [R31-2008000- 10086-0]; Proteogenomic Research Program [2012M3A9B9036679]; National Research Foundation; Ministry of Education, Science and Technology of Korea [ROA-2012-0006262]; Ministry for Health and Welfare Affairs of Korea [A092255]; Gyeonggi Research Development Program; US National Institutes of Health [GM100136]; US National Science Foundation Division of Materials Research [DMR-11-57490]; Kimmel Scholar Award for Cancer Research FX This work was supported by the Global Frontier Project (grants NRF-M1AXA002-20100029785 (S. K.), NRF-M1AXA002-2010-0029765 (Y. H. J.), NRF-2012M3A6A4054271 (J. W. L.) and NRF-2012-054237 (B. W. H.)), the World Class University (grant R31-2008000- 10086-0 (G. H.)), the Proteogenomic Research Program (2012M3A9B9036679 (C. L.)) and by the National Research Foundation funded by the Ministry of Education, Science and Technology of Korea (grant ROA-2012-0006262 (A. M.)). This study was also funded by the Ministry for Health and Welfare Affairs of Korea through the Korea Healthcare Technology Research and Development Project (A092255 (D.-H. N.)) and by a grant from Gyeonggi Research Development Program (S. K.). This work was supported in part by grants from the US National Institutes of Health (GM100136 (M. G.)); the US National Science Foundation Division of Materials Research through DMR-11-57490 (A. G. Marshall, Florida State University); by the state of Florida (M. G.) and by a Kimmel Scholar Award for Cancer Research (M. G.). We appreciate A. G. Marshall for supporting the HDX-MS program and facility, M.-S. Seok (Korea University) for the preparation of the nanodisc and S. W. Lee (Sungkyunkwan University) for X-ray analysis. NR 54 TC 19 Z9 21 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JAN PY 2014 VL 10 IS 1 BP 29 EP U57 DI 10.1038/NCHEMBIO.1381 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 277YJ UT WOS:000328854900007 PM 24212136 ER PT J AU Abtin, A Jain, R Mitchell, AJ Roediger, B Brzoska, AJ Tikoo, S Cheng, Q Ng, LG Cavanagh, LL von Andrian, UH Hickey, MJ Firth, N Weninger, W AF Abtin, Arby Jain, Rohit Mitchell, Andrew J. Roediger, Ben Brzoska, Anthony J. Tikoo, Shweta Cheng, Qiang Ng, Lai Guan Cavanagh, Lois L. von Andrian, Ulrich H. Hickey, Michael J. Firth, Neville Weninger, Wolfgang TI Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection SO NATURE IMMUNOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; GREEN FLUORESCENT PROTEIN; ALPHA-HEMOLYSIN; IN-VIVO; VENULAR WALLS; CELLS; MOUSE; INFLAMMATION; ADAM10; EPIDEMIOLOGY AB Transendothelial migration of neutrophils in postcapillary venules is a key event in the inflammatory response against pathogens and tissue damage. The precise regulation of this process is incompletely understood. We report that perivascular macrophages are critical for neutrophil migration into skin infected with the pathogen Staphylococcus aureus. Using multiphoton intravital microscopy we showed that neutrophils extravasate from inflamed dermal venules in close proximity to perivascular macrophages, which are a major source of neutrophil chemoattractants. The virulence factor alpha-hemolysin produced by S. aureus lyses perivascular macrophages, which leads to decreased neutrophil transmigration. Our data illustrate a previously unrecognized role for perivascular macrophages in neutrophil recruitment to inflamed skin and indicate that S. aureus uses hemolysin-dependent killing of these cells as an immune evasion strategy. C1 [Abtin, Arby; Jain, Rohit; Mitchell, Andrew J.; Roediger, Ben; Tikoo, Shweta; Cavanagh, Lois L.; Weninger, Wolfgang] Centenary Inst, Newtown, NSW, Australia. [Brzoska, Anthony J.; Firth, Neville] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia. [Cheng, Qiang; Hickey, Michael J.] Monash Univ, Monash Med Ctr, Ctr Inflammatory Dis, Dept Med, Clayton, Vic 3800, Australia. [Ng, Lai Guan] Biopolis, Technol & Res A STAR, Agcy Sci, Singapore Immunol Network SIgN, Singapore, Singapore. [Cavanagh, Lois L.] Sydney Med Sch, Sydney, NSW, Australia. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Weninger, Wolfgang] Sydney Med Sch, Discipline Dermatol, Sydney, NSW, Australia. [Weninger, Wolfgang] Royal Prince Alfred Hosp, Dept Dermatol, Camperdown, NSW 2050, Australia. RP Weninger, W (reprint author), Centenary Inst, Newtown, NSW, Australia. EM w.weninger@centenary.org.au RI Mitchell, Andrew/C-2714-2009; Ng, Lai Guan/E-5673-2011; OI Mitchell, Andrew/0000-0003-4454-853X; Ng, Lai Guan/0000-0003-1905-3586; Tikoo, Shweta/0000-0001-5850-8075; Weninger, Wolfgang/0000-0003-3133-8699; /0000-0002-4905-462X; Hickey, Michael/0000-0003-2354-357X FU National Health and Medical Research Council of Australia [1030147] FX We thank M. Willcox (University of New South Wales, Sydney) for S. aureus strains, E. Harry (University of Technology Sydney) for S. aureus USA300, T. Graf (Center for Genomic Regulation, Barcelona, Spain) for providing Lyz2gfp/+ mice, D. Hume (University of Edinburgh) for Csf1r-EGFP mice, M.J. Fraunholz (University of Wurzburg Biocenter) for the pmRFPmars plasmid, A. Smith, S. Allen and S. Dervish for their technical assistance, and M. Rizk and J. Qin for animal husbandry. This work was supported by grant 1030147 from the National Health and Medical Research Council of Australia (to A.A., R.J., N.F. and W.W). NR 42 TC 71 Z9 74 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2014 VL 15 IS 1 BP 45 EP 53 DI 10.1038/ni.2769 PG 9 WC Immunology SC Immunology GA 277DZ UT WOS:000328800500011 PM 24270515 ER PT J AU Chiang, HS Zhao, Y Song, JH Liu, S Wang, NH Terhorst, C Sharpe, AH Basavappa, M Jeffrey, KL Reinecker, HC AF Chiang, Hao-Sen Zhao, Yun Song, Joo-Hye Liu, Song Wang, Ninghai Terhorst, Cox Sharpe, Arlene H. Basavappa, Megha Jeffrey, Kate L. Reinecker, Hans-Christian TI GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses SO NATURE IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTOR-3; RIG-I; VIRUS-INFECTION; INNATE IMMUNITY; ACTIN CYTOSKELETON; SIGNALING PATHWAY; DENDRITIC CELLS; EXCHANGE FACTOR AB Detailed understanding of the signaling intermediates that confer the sensing of intracellular viral nucleic acids for induction of type I interferons is critical for strategies to curtail viral mechanisms that impede innate immune defenses. Here we show that the activation of the microtubule-associated guanine nucleotide exchange factor GEE-H1, encoded by Arhgef2, is essential for sensing of foreign RNA by RIG-I-like receptors. Activation of GEE-H1 controls RIG-I-dependent and Mda5-dependent phosphorylation of IRF3 and induction of IFN-beta expression in macrophages. Generation of Arhgef2(-/-) mice revealed a pronounced signaling defect that prevented antiviral host responses to encephalomyocarditis virus and influenza A virus. Microtubule networks sequester GEF-H1 that upon activation is released to enable antiviral signaling by intracellular nucleic acid detection pathways. C1 [Chiang, Hao-Sen; Zhao, Yun; Song, Joo-Hye; Liu, Song; Basavappa, Megha; Jeffrey, Kate L.; Reinecker, Hans-Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Chiang, Hao-Sen; Zhao, Yun; Song, Joo-Hye; Liu, Song; Basavappa, Megha; Jeffrey, Kate L.; Reinecker, Hans-Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Wang, Ninghai; Terhorst, Cox] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02215 USA. [Wang, Ninghai; Terhorst, Cox] Harvard Univ, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol, Boston, MA USA. RP Reinecker, HC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. EM hans-christian_reinecker@hms.harvard.edu OI CHIANG, HAO-SEN/0000-0001-5041-9705 FU US National Institutes of Health [AI-093588, DK-068181, DK-033506, DK-043351, DK-52510] FX This work was supported by grants AI-093588 (H.-C.R.), DK-068181 (H.-C.R.), DK-033506 (H.-C.R.), DK-043351 (H.-C.R. and C.T.) and DK-52510 (C.T.) from the US National Institutes of Health. NR 50 TC 9 Z9 9 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2014 VL 15 IS 1 BP 63 EP 71 DI 10.1038/ni.2766 PG 9 WC Immunology SC Immunology GA 277DZ UT WOS:000328800500013 PM 24270516 ER PT J AU McFarland, AP Horner, SM Jarret, A Joslyn, RC Bindewald, E Shapiro, BA Delker, DA Hagedorn, CH Carrington, M Gale, M Savan, R AF McFarland, Addle P. Horner, Stacy M. Jarret, Abigail Joslyn, Rochelle C. Bindewald, Eckart Shapiro, Bruce A. Delker, Don A. Hagedorn, Curt H. Carrington, Mary Gale, Michael, Jr. Savan, Ram TI The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs SO NATURE IMMUNOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; IL28B GENOTYPE; SECONDARY STRUCTURE; ANTIVIRAL DEFENSES; INTERFERON-LAMBDA; INNATE IMMUNITY; EXPRESSION; INFECTION; CLEARANCE AB IFNL3, which encodes interferon-lambda 3 (IFN-lambda 3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance of HCV. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) in the 3' untranslated region (UTR) of IFNL3 mRNA that dictated transcript stability. We found that this polymorphism influenced AU-rich element (ARE)-mediated decay (AMD) of IFNL3 mRNA, as well as the binding of HCV-induced microRNAs during infection. Together these pathways mediated robust repression of the unfavorable IFNL3 polymorphism. Our data reveal a previously unknown mechanism by which HCV attenuates the antiviral response and indicate new potential therapeutic targets for HCV treatment. C1 [McFarland, Addle P.; Horner, Stacy M.; Jarret, Abigail; Joslyn, Rochelle C.; Gale, Michael, Jr.; Savan, Ram] Univ Washington, Dept Immunol, Seattle, WA 98195 USA. [Bindewald, Eckart] Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA. [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Delker, Don A.; Hagedorn, Curt H.] Univ Utah, Sch Med, Div Gastroenterol Hepatol & Nutr, Salt Lake City, UT USA. [Carrington, Mary] Frederick Natl Lab Canc Res, Sci Applicat Int Corp Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. [Carrington, Mary] MIT, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA. [Carrington, Mary] Harvard Univ, Boston, MA 02115 USA. RP Savan, R (reprint author), Univ Washington, Dept Immunol, Seattle, WA 98195 USA. EM savanram@uw.edu OI Gale, Michael/0000-0002-6332-7436 FU Department of Immunology of the University of Washington; US National Institutes of Health [AI060389, AI88778, CA148068]; Frederick National Laboratory for Cancer Research of the US National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the US National Institutes of Health, Frederick National Laboratory for Cancer Research and the National Cancer Institute, Center for Cancer Research FX We thank P. Fink, D. Stetson, E. Clark and C. Lim for critical reading of the manuscript, and S. Badil and M. Hong for technical assistance. Supported by the Department of Immunology of the University of Washington (R.S.), the US National Institutes of Health (AI060389 and AI88778 to M.G., and CA148068 to C.H.H.) and federal funds from the Frederick National Laboratory for Cancer Research of the US National Institutes of Health (HHSN261200800001E) and the Intramural Research Program of the US National Institutes of Health, Frederick National Laboratory for Cancer Research and the National Cancer Institute, Center for Cancer Research (E.B., B.A.S. and M.C.). NR 45 TC 56 Z9 56 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2014 VL 15 IS 1 BP 72 EP 79 DI 10.1038/ni.2758 PG 8 WC Immunology SC Immunology GA 277DZ UT WOS:000328800500014 PM 24241692 ER PT J AU Raj, A McVicker, G AF Raj, Anil McVicker, Graham TI The genome shows its sensitive side SO NATURE METHODS LA English DT Editorial Material ID OPEN CHROMATIN AB New methods for measuring the sensitivity of chromatin to DNase digestion and Tn5 transposition help us map and interpret the genome's regulatory sequences. C1 [Raj, Anil; McVicker, Graham] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [McVicker, Graham] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Raj, A (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA. EM mcvicker@jimmy.harvard.edu NR 9 TC 0 Z9 0 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JAN PY 2014 VL 11 IS 1 BP 39 EP 40 DI 10.1038/nmeth.2770 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 282NI UT WOS:000329178200022 PM 24378702 ER PT J AU He, HH Meyer, CA Hu, SS Chen, MW Zang, CZ Liu, Y Rao, PK Fei, T Xu, H Long, H Liu, XS Brown, M AF He, Housheng Hansen Meyer, Clifford A. Hu, Sheng'en Shawn Chen, Mei-Wei Zang, Chongzhi Liu, Yin Rao, Prakash K. Fei, Teng Xu, Han Long, Henry Liu, X. Shirley Brown, Myles TI Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification SO NATURE METHODS LA English DT Article ID CHROMATIN ACCESSIBILITY; REGULATORY ELEMENTS; HUMAN GENOME; SPECIFICITY; NUCLEOSOME; EXPRESSION; DYNAMICS; INSIGHTS; SCALE; STATE AB Sequencing of DNase I hypersensitive sites (DNase-seq) is a powerful technique for identifying cis-regulatory elements across the genome. We studied the key experimental parameters to optimize performance of DNase-seq. Sequencing short fragments of 50-100 base pairs (bp) that accumulate in long internucleosome linker regions was more efficient for identifying transcription factor binding sites compared to sequencing longer fragments. We also assessed the potential of DNase-seq to predict transcription factor occupancy via generation of nucleotide-resolution transcription factor footprints. In modeling the sequence-specific DNase I cutting bias, we found a strong effect that varied over more than two orders of magnitude. This indicates that the nucleotideresolution cleavage patterns at many transcription factor binding sites are derived from intrinsic DNase I cleavage bias rather than from specific protein-DNA interactions. In contrast, quantitative comparison of DNase I hypersensitivity between states can predict transcription factor occupancy associated with particular biological perturbations. C1 [He, Housheng Hansen; Meyer, Clifford A.; Zang, Chongzhi; Fei, Teng; Xu, Han; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Meyer, Clifford A.; Zang, Chongzhi; Fei, Teng; Xu, Han; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [He, Housheng Hansen; Fei, Teng; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng Hansen; Fei, Teng; Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [He, Housheng Hansen; Meyer, Clifford A.; Hu, Sheng'en Shawn; Chen, Mei-Wei; Zang, Chongzhi; Liu, Yin; Rao, Prakash K.; Fei, Teng; Xu, Han; Long, Henry; Liu, X. Shirley; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [He, Housheng Hansen] Univ Hlth Network, Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON, Canada. [He, Housheng Hansen] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hu, Sheng'en Shawn; Liu, Yin] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM henry_long@dfci.harvard.edu; xsliu@jimmy.harvard.edu; myles_brown@dfci.harvard.edu RI Fei, Teng/G-5324-2015; Zang, Chongzhi/D-1445-2011; OI Fei, Teng/0000-0001-5707-0673; Brown, Myles/0000-0002-8213-1658 FU US National Institutes of Health [1R01 GM099409, 1U41 HG007000, 2P50 CA090381-062, R01 DK074967-06, 1K99CA172948-01] FX This work was supported by grants from the US National Institutes of Health (1R01 GM099409 to X. S. L.; 1U41 HG007000 to X. S. L. and C. A. M.; 2P50 CA090381-06 to C. A. M. and M. B.; 2R01 DK074967-06 to M. B. and X. S. L., 1K99CA172948-01 to H. H. H.); the Mazzone Award (to X. S. L.), the Department of Defense (W81XWH-10-1-0557 to H. H. H.) and the Prostate Cancer Foundation (to M. B.). NR 22 TC 48 Z9 49 U1 5 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JAN PY 2014 VL 11 IS 1 BP 73 EP + DI 10.1038/NEMTH.2762 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 282NI UT WOS:000329178200030 PM 24317252 ER PT J AU Hemler, ME AF Hemler, Martin E. TI Tetraspanin proteins promote multiple cancer stages SO NATURE REVIEWS CANCER LA English DT Review ID LYMPH-NODE METASTASIS; HUMAN COLON-CARCINOMA; LAMININ-BINDING INTEGRINS; IN-VIVO; PROSTATE-CANCER; CELL-SURFACE; BREAST-CANCER; MONOCLONAL-ANTIBODIES; GROWTH-FACTOR; ENRICHED MICRODOMAINS AB An abundance of evidence shows supporting roles for tetraspanin proteins in human cancer. Many studies show that the expression of tetraspanins correlates with tumour stage, tumour type and patient outcome. In addition, perturbations of tetraspanins in tumour cell lines can considerably affect cell growth, morphology, invasion, tumour engraftment and metastasis. This Review emphasizes new studies that have used de novo mouse cancer models to show that select tetraspanin proteins have key roles in tumour initiation, promotion and metastasis. This Review also emphasizes how tetraspanin proteins can sometimes participate in tumour angiogenesis. These recent data build an increasingly strong case for tetraspanins as therapeutic targets. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM Martin_Hemler@DFCI.Harvard.EDU FU US National Institutes of Health (NIH) [CA42368] FX The author is supported by US National Institutes of Health (NIH) grant CA42368. NR 185 TC 59 Z9 63 U1 5 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2014 VL 14 IS 1 BP 49 EP 60 DI 10.1038/nrc3640 PG 12 WC Oncology SC Oncology GA 280LG UT WOS:000329030700012 PM 24505619 ER PT J AU Magnain, C Augustinack, JC Reuter, M Wachinger, C Frosch, MP Ragan, T Akkin, T Wedeen, VJ Boas, DA Fischl, B AF Magnain, Caroline Augustinack, Jean C. Reuter, Martin Wachinger, Christian Frosch, Matthew P. Ragan, Timothy Akkin, Taner Wedeen, Van J. Boas, David A. Fischl, Bruce TI Blockface histology with optical coherence tomography: A comparison with Nissl staining SO NEUROIMAGE LA English DT Article DE OCT; Cytoarchitecture; Histology; Registration ID HUMAN CEREBRAL-CORTEX; MICROSTRUCTURAL PARCELLATION; HUMAN BRAIN; MICROSCOPY; CYTOARCHITECTURE; MRI; REGISTRATION; CONTRAST AB Spectral domain optical coherence tomography (SD-OCT) is a high resolution imaging technique that generates excellent contrast based on intrinsic optical properties of the tissue, such as neurons and fibers. The SD-OCT data acquisition is performed directly on the tissue block, diminishing the need for cutting, mounting and staining. We utilized SD-OCT to visualize the laminar structure of the isocortex and compared cortical cytoarchitecture with the gold standard Nissl staining, both qualitatively and quantitatively. In histological processing, distortions routinely affect registration to the blockface image and prevent accurate 3D reconstruction of regions of tissue. We compared blockface registration to SD-OCT and Nissl, respectively, and found that SD-OCT-blocicface registration was significantly more accurate than Nissl-blocicface registration. Two independent observers manually labeled cortical laminae (e.g. III, IV and V) in SD-OCT images and Nissl stained sections. Our results show that OCT images exhibit sufficient contrast in the cortex to reliably differentiate the cortical layers. Furthermore, the modalities were compared with regard to cortical laminar organization and showed good agreement. Taken together, these SD-OCT results suggest that SD-OCT contains information comparable to standard histological stains such as Nissl in terms of distinguishing cortical layers and architectonic areas. Given these data, we propose that SD-OCT can be used to reliably generate 3D reconstructions of multiple cubic centimeters of cortex that can be used to accurately and semi-automatically perform standard histological analyses. (C) 2013 Elsevier Inc. All rights reserved. C1 [Magnain, Caroline; Augustinack, Jean C.; Wedeen, Van J.; Boas, David A.; Fischl, Bruce] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Reuter, Martin; Wachinger, Christian] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Pathol Serv, CS Kubik Lab Neuropathol, Boston, MA 02115 USA. [Reuter, Martin; Wachinger, Christian; Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Ragan, Timothy] TissueVision Inc, Cambridge, MA 02139 USA. [Akkin, Taner] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. RP Magnain, C (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Reuter, Martin/B-3456-2010; Christian, Wachinger/L-7358-2016 OI Reuter, Martin/0000-0002-2665-9693; Christian, Wachinger/0000-0002-3652-1874 FU National Center for Research Resources [P41-RR14075, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [AG022381, 5R01AG008122-22, K01AG028521]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, 1S10RR023401, 1S10RR019307, 1S10RR023043]; Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765] FX Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381, 5R01AG008122-22, K01AG028521), the National Center for Alternative Medicine (RC1 AT005728-01), and the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963), and was made possible by the resources provided by the Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism 82 Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. NR 39 TC 22 Z9 22 U1 1 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2014 VL 84 BP 524 EP 533 DI 10.1016/j.neuroimage.2013.08.072 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DF UT WOS:000328868600048 PM 24041872 ER PT J AU Tak, S Wang, DJJ Polimeni, JR Yan, LR Chen, JJ AF Tak, Sungho Wang, Danny J. J. Polimeni, Jonathan R. Yan, Lirong Chen, J. Jean TI Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal SO NEUROIMAGE LA English DT Article DE Cerebral blood flow (CBF); Resting-state BOLD; Arterial-spin labeling (ASL); MR angiography; Blood volume fraction ID CEREBRAL-BLOOD-FLOW; PHYSIOLOGICAL NOISE CORRECTION; INFRARED SPECTROSCOPY NIRS; LABELING FUNCTIONAL MRI; SURFACE-BASED ANALYSIS; HUMAN BRAIN; 7 T; OXYGEN-CONSUMPTION; VISUAL-STIMULATION; CONCURRENT FMRI AB Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity. (C) 2013 Elsevier Inc. All rights reserved. C1 [Tak, Sungho; Chen, J. Jean] Univ Toronto, Baycrest Ctr, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Wang, Danny J. J.; Yan, Lirong] Univ Calif Los Angeles, Dept Neurol, Lab Funct MRI Technol LOFT, Los Angeles, CA 90095 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Tak, S (reprint author), Baycrest Ctr Geriatr Care, Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM stak@research.baycrest.org RI Polimeni, Jonathan/P-1395-2014 OI Polimeni, Jonathan/0000-0002-1348-1179 FU Natural Sciences and Engineering Council of Canada (NSERC); National Institutes of Health (NIH) [P50-HD-055784, R01-MH080892, R01-NS081077, R01-EB014922]; Rotman Research Institute of Baycrest; Heart and Stroke Foundation Centre for Stroke Recovery FX This research was supported by the Natural Sciences and Engineering Council of Canada (NSERC) grant, the National Institutes of Health (NIH) grants P50-HD-055784, R01-MH080892, R01-NS081077, and R01-EB014922, as well as by fellowship funding from the Rotman Research Institute of Baycrest and Heart and Stroke Foundation Centre for Stroke Recovery (S. Talc). NR 67 TC 10 Z9 10 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2014 VL 84 BP 672 EP 680 DI 10.1016/j.neuroimage.2013.09.057 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 278DF UT WOS:000328868600061 PM 24099842 ER PT J AU Mills, KA Starr, PA Ostrem, JL AF Mills, Kelly A. Starr, Philip A. Ostrem, Jill L. TI Neuromodulation for Dystonia: Target and Patient Selection SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Deep brain stimulation; Globus pallidus; Subthalamic nucleus; Brain target; Outcomes; Predictive factors ID DEEP-BRAIN-STIMULATION; GLOBUS-PALLIDUS INTERNUS; PRIMARY GENERALIZED DYSTONIA; PRIMARY CERVICAL DYSTONIA; TERM-FOLLOW-UP; QUALITY-OF-LIFE; KINASE-ASSOCIATED NEURODEGENERATION; PRIMARY TORSION DYSTONIA; FOCAL HAND DYSTONIA; MEIGE-SYNDROME AB Treatment of dystonia refractory to oral medications or botulinum toxin injections includes the use of deep brain stimulation (DBS). Expectations should be established based on patient-related factors, including type of dystonia, genetic cause, target symptoms, age at the time of surgery, disease duration, or the presence of fixed skeletal deformities. Premorbid conditions such as psychiatric illness and cognitive impairment should be considered. Target selection is an emerging issue in DBS for dystonia. Although efficacy has been established for targeting the globus pallidus internus for dystonia, other brain targets such as the subthalamic nucleus, thalamus, or cortex may be promising alternatives. C1 [Mills, Kelly A.; Ostrem, Jill L.] San Francisco VA Med Ctr, UCSF Dept Neurol, PADRECC, San Francisco, CA 94143 USA. [Starr, Philip A.] San Francisco VA Med Ctr, UCSF Dept Neurosurg, PADRECC, San Francisco, CA 94143 USA. RP Starr, PA (reprint author), San Francisco VA Med Ctr, UCSF Dept Neurosurg, PADRECC, Box 1838,1635 Divisadero St,Suite 520, San Francisco, CA 94143 USA. EM StarrP@neurosurg.ucsf.edu NR 127 TC 10 Z9 10 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 EI 1558-1349 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 2014 VL 25 IS 1 BP 59 EP + DI 10.1016/j.nec.2013.08.014 PG 18 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 278VS UT WOS:000328918600009 PM 24262900 ER PT J AU Aronson, JP Katnani, HA Eskandar, EN AF Aronson, Joshua P. Katnani, Husam A. Eskandar, Emad N. TI Neuromodulation for Obsessive-Compulsive Disorder SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Obsessive-compulsive disorder; Deep brain stimulation; Neuromodulation; Vagus nerve stimulation; Transcranial magnetic stimulation ID DEEP BRAIN-STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; VAGUS NERVE-STIMULATION; CEREBRAL-BLOOD-FLOW; TERM-FOLLOW-UP; ANTERIOR CINGULATE CORTEX; GLUCOSE METABOLIC RATES; STEREOTAXIC SUBCAUDATE TRACTOTOMY; SUBTHALAMIC NUCLEUS STIMULATION; POSITRON-EMISSION-TOMOGRAPHY AB This article describes the basis for neuromodulation procedures for obsessive-compulsive disorder (OCD) and summarizes the literature on the efficacy of these interventions. Discussion includes neural circuitry underlying OCD pathology, the history and types of ablative procedures, the targets and modalities used for neuromodulation, and future therapeutic directions. C1 [Aronson, Joshua P.; Katnani, Husam A.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM eeskandar@partners.org NR 150 TC 2 Z9 2 U1 3 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 EI 1558-1349 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 2014 VL 25 IS 1 BP 85 EP + DI 10.1016/j.nec.2013.08.003 PG 18 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 278VS UT WOS:000328918600011 PM 24262902 ER PT J AU Bachelerie, F Ben-Baruch, A Burkhardt, AM Combadiere, C Farber, JM Graham, GJ Horuk, R Sparre-Ulrich, AH Locati, M Luster, AD Mantovani, A Matsushima, K Murphy, PM Nibbs, R Nomiyama, H Power, CA Proudfoot, AEI Rosenkilde, MM Rot, A Sozzani, S Thelen, M Yoshie, O Zlotnik, A AF Bachelerie, Francoise Ben-Baruch, Adit Burkhardt, Amanda M. Combadiere, Christophe Farber, Joshua M. Graham, Gerard J. Horuk, Richard Sparre-Ulrich, Alexander Hovard Locati, Massimo Luster, Andrew D. Mantovani, Alberto Matsushima, Kouji Murphy, Philip M. Nibbs, Robert Nomiyama, Hisayuki Power, Christine A. Proudfoot, Amanda E. I. Rosenkilde, Mette M. Rot, Antal Sozzani, Silvano Thelen, Marcus Yoshie, Osamu Zlotnik, Albert TI International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PROTEIN-COUPLED RECEPTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; REGULATORY T-CELLS; SARCOMA-ASSOCIATED HERPESVIRUS; MACROPHAGE-DERIVED CHEMOKINE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HIGH-AFFINITY BINDING; MESSENGER-RNA EXPRESSION; DUFFY ANTIGEN RECEPTOR; CENTRAL-NERVOUS-SYSTEM AB Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52: 145-176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U. S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee. C1 [Bachelerie, Francoise] Univ Paris 11, LERMIT, INSERM, UMR S996, Clamart, France. [Ben-Baruch, Adit] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Burkhardt, Amanda M.; Zlotnik, Albert] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA. [Combadiere, Christophe] Univ Paris 06, Lab Immunol Cellulaire, INSERM, UMR S 945, Paris, France. [Farber, Joshua M.; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Graham, Gerard J.; Nibbs, Robert] Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow Biomed Res Ctr, Glasgow, Lanark, Scotland. [Horuk, Richard] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. [Sparre-Ulrich, Alexander Hovard; Rosenkilde, Mette M.] Univ Copenhagen, Mol Pharmacol Lab, Dept Neurosci & Pharmacol, Fac Hlth & Med Sci, Copenhagen, Denmark. [Locati, Massimo; Mantovani, Alberto] Univ Milan, Milan, Italy. [Locati, Massimo; Mantovani, Alberto] Humanitas Clin & Res Inst, Rozzano, Italy. [Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. [Matsushima, Kouji] Univ Tokyo, Sch Med, Dept Mol Prevent Med, Tokyo 113, Japan. [Nomiyama, Hisayuki] Kumamoto Univ, Dept Mol Enzymol, Grad Sch Med Sci, Kumamoto, Japan. [Power, Christine A.] Merck Serono SA, Geneva Res Ctr, Geneva, Switzerland. [Proudfoot, Amanda E. I.] NovImmune SA, Geneva, Switzerland. [Rot, Antal] Univ Birmingham, Med Res Council, Ctr Immune Regulat, Inst Biomed Res,Sch Infect & Immun, Birmingham, W Midlands, England. [Sozzani, Silvano] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy. [Sozzani, Silvano] Humanitas Clin & Res Ctr, Rozzano, Italy. [Thelen, Marcus] Inst Res Biomed, Bellinzona, Switzerland. [Yoshie, Osamu] Kinki Univ, Dept Microbiol, Fac Med, Osaka, Japan. RP Murphy, PM (reprint author), NIH, Nomenclature Comm Int Union Pharmacol, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov RI Combadiere, Christophe/I-5639-2013; Locati, Massimo/H-8404-2015; BACHELERIE, FRANCOISE/F-8823-2013; OI Combadiere, Christophe/0000-0002-1755-4531; Locati, Massimo/0000-0003-3077-590X; Mantovani, Alberto/0000-0001-5578-236X; Sozzani, Silvano/0000-0002-3144-8743 FU Intramural Research Program of the National Institutes of Health [National Institute of Allergy and Infectious Diseases] FX This work was supported by the Intramural Research Program of the National Institutes of Health [National Institute of Allergy and Infectious Diseases]. NR 1100 TC 138 Z9 139 U1 7 U2 50 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD JAN PY 2014 VL 66 IS 1 BP 1 EP 79 DI 10.1124/pr.113.007724 PG 79 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 276NL UT WOS:000328756900001 PM 24218476 ER PT J AU Eberlin, KR Chang, J Curtin, CM Sammer, DM Saint-Cyr, M Taghinia, AH AF Eberlin, Kyle R. Chang, James Curtin, Catherine M. Sammer, Douglas M. Saint-Cyr, Michel Taghinia, Amir H. TI Soft-Tissue Coverage of the Hand: A Case-Based Approach SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RADIAL FOREARM FLAP; CROSS-FINGER FLAP; POSTERIOR INTEROSSEOUS ARTERY; HOMODIGITAL ISLAND FLAP; DERMAL REGENERATION TEMPLATE; DONOR SITE MORBIDITY; TOE PULP TRANSFER; LATERAL ARM FLAP; 1ST WEB SPACE; THUMB RECONSTRUCTION AB Adequate soft-tissue coverage of the hand is paramount to achieve optimal aesthetic and functional results in patients with complex hand defects. In this article, the authors present four illustrative clinical cases and discuss potential reconstructive modalities. For each scenario, two surgical options are discussed: one established and one nontraditional method of reconstruction. The authors' preferred method and technical pearls for execution are presented. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02115 USA. Stanford Univ, Sch Med, Div Plast & Reconstruct Surg, Stanford, CA 94305 USA. Univ Texas SW Med Ctr Dallas, Dept Plast Surg, Dallas, TX USA. Mayo Clin, Div Plast Surg, Rochester, MN USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. RP Taghinia, AH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Plast Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM amir.taghinia@childrens.harvard.edu OI Curtin, Catherine/0000-0003-0850-9277 NR 78 TC 2 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2014 VL 133 IS 1 BP 91 EP 101 DI 10.1097/01.prs.0000436831.73323.88 PG 11 WC Surgery SC Surgery GA 282IQ UT WOS:000329164900044 PM 24105089 ER PT J AU Waxmonsky, J Kilbourne, AM Goodrich, DE Nord, KM Lai, ZS Laird, C Clogston, J Kim, HM Miller, C Bauer, MS AF Waxmonsky, Jeanette Kilbourne, Amy M. Goodrich, David E. Nord, Kristina M. Lai, Zongshan Laird, Christina Clogston, Julia Kim, Hyungjin Myra Miller, Christopher Bauer, Mark S. TI Enhanced Fidelity to Treatment for Bipolar Disorder: Results From a Randomized Controlled Implementation Trial SO PSYCHIATRIC SERVICES LA English DT Article ID HIV PREVENTION INTERVENTIONS; ALCOHOL-USE DISORDERS; COLLABORATIVE CARE; SERVICE PROVIDERS; PARIHS FRAMEWORK; CLINICAL-TRIALS; CHRONIC ILLNESS; RISK DRINKING; AUDIT-C; PROGRAM AB Objective: The authors compared fidelity to bipolar disorder treatment at community practices that received a standard or enhanced version of a novel implementation intervention called Replicating Effective Programs (REP). Methods: Five community practices in Michigan and Colorado were assigned at random to receive enhanced (N=3) or standard (N=2) REP to help implement Life Goals Collaborative Care (LGCC), a psychosocial intervention consisting of four self-management support group sessions, ongoing care management contacts by phone, and dissemination of guidelines to providers. Standard REP includes an intervention package consisting of an outline, a treatment manual and implementation guide, a standard training program, and as-needed technical assistance. Enhanced REP added customization of the treatment manual and ongoing, proactive technical assistance from internal and external facilitators. Multiple and logistic regression analyses determined the impact of enhanced versus standard REP on patient-level fidelity. Results: The participants (N=384) had a mean age of 42 years; 67% were women, and 30% were nonwhite. Participants attended an average of three group sessions and had an average of four care management contacts. After adjustment for patient factors, enhanced REP was associated with 2.6 (p<.001) times more total sessions and contacts than standard REP, which was driven by 2.5 (p<.01) times more care management contacts. Women and participants with a history of homelessness had fewer total sessions and contacts. Conclusions: Enhanced REP was associated with improved LGCC fidelity, primarily for care management contacts. Additional customization of interventions such as LGCC may be needed to ensure adequate treatment fidelity for vulnerable populations. C1 [Waxmonsky, Jeanette] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. [Kilbourne, Amy M.; Goodrich, David E.; Nord, Kristina M.; Lai, Zongshan; Clogston, Julia; Kim, Hyungjin Myra] Vet Affairs VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Kim, Hyungjin Myra] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. [Laird, Christina] VA Eastern Colorado Healthcare Syst, Denver, CO USA. [Miller, Christopher; Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. RP Kilbourne, AM (reprint author), Vet Affairs VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. EM amykilbo@umich.edu OI Goodrich, David/0000-0003-3232-2189 FU National Institute of Mental Health; Health Services Research and Development Service, Veterans Health Administration, Department of Veterans Affairs (VA) FX This work was supported by the National Institute of Mental Health and the Health Services Research and Development Service, Veterans Health Administration, Department of Veterans Affairs (VA). The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. NR 33 TC 10 Z9 10 U1 1 U2 13 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2014 VL 65 IS 1 BP 81 EP 90 DI 10.1176/appi.ps.201300039 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 280CB UT WOS:000329005200013 PM 24129806 ER PT J AU Robles, TF Slatcher, RB Trombello, JM McGinn, MM AF Robles, Theodore F. Slatcher, Richard B. Trombello, Joseph M. McGinn, Meghan M. TI Marital Quality and Health: A Meta-Analytic Review SO PSYCHOLOGICAL BULLETIN LA English DT Review DE marriage; marital quality; health; mortality; meta-analysis ID AMBULATORY BLOOD-PRESSURE; CORONARY-HEART-DISEASE; LESBIAN COHABITING COUPLES; AFRICAN-AMERICAN COUPLES; LEFT-VENTRICULAR MASS; TRAIT NEGATIVE AFFECT; SURROGATE END-POINTS; SELF-RATED HEALTH; MIDDLE-AGED WOMEN; PHYSICAL HEALTH AB This meta-analysis reviewed 126 published empirical articles over the past 50 years describing associations between marital relationship quality and physical health in more than 72,000 individuals. Health outcomes included clinical endpoints (objective assessments of function, disease severity, and mortality; subjective health assessments) and surrogate endpoints (biological markers that substitute for clinical endpoints, such as blood pressure). Biological mediators included cardiovascular reactivity and hypothalamic-pituitary-adrenal axis activity. Greater marital quality was related to better health, with mean effect sizes from r = .07 to.21, including lower risk of mortality (r = .11) and lower cardiovascular reactivity during marital conflict (r = -.13), but not daily cortisol slopes or cortisol reactivity during conflict. The small effect sizes were similar in magnitude to previously found associations between health behaviors (e. g., diet) and health outcomes. Effect sizes for a small subset of clinical outcomes were susceptible to publication bias. In some studies, effect sizes remained significant after accounting for confounds such as age and socioeconomic status. Studies with a higher proportion of women in the sample demonstrated larger effect sizes, but we found little evidence for gender differences in studies that explicitly tested gender moderation, with the exception of surrogate endpoint studies. Our conclusions are limited by small numbers of studies for specific health outcomes, unexplained heterogeneity, and designs that limit causal inferences. These findings highlight the need to explicitly test affective, health behavior, and biological mechanisms in future research, and focus on moderating factors that may alter the relationship between marital quality and health. C1 [Robles, Theodore F.; Trombello, Joseph M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Slatcher, Richard B.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. [McGinn, Meghan M.] Vet Affairs Puget Sound Healthcare Syst, Mental Illness Res Educ & Clin Care, Seattle, WA USA. RP Robles, TF (reprint author), Univ Calif Los Angeles, Dept Psychol, Box 951563,1285 Franz Hall, Los Angeles, CA 90095 USA. EM robles@psych.ucla.edu FU William T. Grant Foundation [9333]; National Institutes of Health [R21 AG032494, T32 MH015750, R01 HL114097, F31 AG034718]; Department of Veterans Affairs Office of Academic Affiliations; Advanced Fellowship Program in Mental Illness Research and Treatment; Veterans Affairs Puget Sound Healthcare System, Seattle, Washington FX This research was supported by William T. Grant Foundation Research Grant 9333 and National Institutes of Health Grants R21 AG032494 (to Theodore F. Robles), T32 MH015750 and R01 HL114097 (to Richard B. Slatcher), and F31 AG034718 (to Meghan M. McGinn). The work of Meghan M. McGinn was also supported by resources from the Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, and the Veterans Affairs Puget Sound Healthcare System, Seattle, Washington. We thank the article authors who sent us additional statistics to allow us to compute effect sizes; Blair Ibarra, Emily Kelleher, Jennifer Linchey, and Meera Parbhakar for collecting citations; Julianne Holt-Lunstad and Annemarie Cano for supportive consultation; and graduate students and postdoctoral trainees in the UCLA Relationships and Health Laboratory and Tom Bradbury for comments on drafts of this article. NR 321 TC 92 Z9 95 U1 12 U2 76 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 EI 1939-1455 J9 PSYCHOL BULL JI Psychol. Bull. PD JAN PY 2014 VL 140 IS 1 BP 140 EP 187 DI 10.1037/a0031859 PG 48 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 280QB UT WOS:000329044700008 PM 23527470 ER PT J AU Zhang, XY Chen, DC Tan, YL Xiu, MH Cui, JY Hui, L Yang, FD Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Tan, Yun Long Xiu, Mei Hong Cui, Jingyi Hui, Li Yang, Fu De Kosten, Thomas R. TI Socio-demographic and clinical characteristics of heavy and non-heavy smokers among schizophrenia inpatients in a Chinese Han population SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Smoking; Cigarettes; Heavy; Psychopathology; Side effects ID CIGARETTE-SMOKING; NICOTINE DEPENDENCE; MENTAL-ILLNESS; ANTIPSYCHOTIC MEDICATIONS; NONPSYCHIATRIC CONTROLS; CARDIOVASCULAR-DISEASE; TOBACCO SMOKING; USE DISORDERS; SUBSTANCE USE; SEVERITY AB Despite higher smoking rates in schizophrenia, few studies have explored the clinical-demographic correlates of different amounts of smoking exposure. Little is known about the association between smoking severity and clinical phenotypes in Chinese patients with schizophrenia. We investigated differences between heavy (a parts per thousand yen1 pack/day) and non-heavy (< 1 pack/day) smoking in 550 male inpatients with schizophrenia using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence. They also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS), as well as were assayed with laboratory tests and an electrocardiogram. Heavy smoking prevalence was approximately 31 %. Compared to the non-heavy smokers, the heavy smokers were younger, more with paranoid subtype but less with disorganized subtype schizophrenia, smoked at an earlier age, fewer getting clozapine or all atypical antipsychotics together, and were taking larger doses of antipsychotic drugs. The heavy smokers scored significantly lower on the PANSS negative symptom subscore and total score, and also on the SAES and AIMS scores than the non-heavy smokers. In addition, heavy smokers displayed longer rate-corrected electrocardiographic QT intervals, but without any significant differences in other laboratory tests. Our results suggest several clinical or demographic differences between the heavy and non-heavy smoking patients with schizophrenia in a Chinese population. Heavy smoking remains a general health risk for schizophrenia. C1 [Zhang, Xiang Yang; Chen, Da Chun; Tan, Yun Long; Xiu, Mei Hong; Cui, Jingyi; Hui, Li; Yang, Fu De] Beijing HuiLongGuan Hosp, Beijing 100096, Peoples R China. [Zhang, Xiang Yang; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang] VA Med Ctr, Houston, TX 77030 USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu FU Beijing Municipal Natural Science Foundation [7132063]; Stanley Medical Research Institute [03T-459, 05T-726]; United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by the Beijing Municipal Natural Science Foundation, 7132063, the Stanley Medical Research Institute (03T-459 and 05T-726), and the United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639. NR 67 TC 4 Z9 5 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2014 VL 231 IS 1 BP 305 EP 314 DI 10.1007/s00213-013-3239-x PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 281NI UT WOS:000329107900029 PM 23963531 ER PT J AU Gross, AF Stern, TA AF Gross, Anne F. Stern, Theodore A. TI Neuropsychiatric Conditions Associated With Anesthesia Exposure SO PSYCHOSOMATICS LA English DT Review ID POSTOPERATIVE COGNITIVE DYSFUNCTION; ARTERY-BYPASS-SURGERY; GENERAL-ANESTHESIA; NONCARDIAC SURGERY; ALZHEIMERS-DISEASE; INTRAOPERATIVE AWARENESS; BISPECTRAL INDEX; ELDERLY-PATIENTS; EXPLICIT RECALL; NERVOUS-SYSTEM AB Background: Although anesthetics have been used for more than a century, their mechanisms of action remain poorly understood. Given that a number of intraoperative and postoperative neuropsychiatric syndromes have been linked to the use of anesthetics, practitioners should familiarize themselves with these conditions. Methods: Basic concepts about anesthesia are reviewed and neuropsychiatric syndromes associated with anesthesia exposure described. Conclusions: Emergence delirium, postoperative delirium, postoperative cognitive dysfunction, and intraoperative awareness can develop in association with use of inhalation anesthetics and intravenously administered anesthetics'. C1 [Gross, Anne F.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gross, AF (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. EM gross@ohsu.edu NR 73 TC 1 Z9 2 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2014 VL 55 IS 1 BP 21 EP 28 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 281SP UT WOS:000329121600002 PM 24070660 ER PT J AU Ajmal, A Joffe, H Nachtigall, LB AF Ajmal, Adnan Joffe, Hadine Nachtigall, Lisa B. TI Psychotropic-Induced Hyperprolactinemia: A Clinical Review SO PSYCHOSOMATICS LA English DT Review ID ANTIPSYCHOTIC-INDUCED HYPERPROLACTINEMIA; DOPAMINE-D-2 RECEPTOR OCCUPANCY; POSITRON-EMISSION-TOMOGRAPHY; PROLACTIN LEVELS; ATYPICAL ANTIPSYCHOTICS; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; SCHIZOPHRENIC-PATIENTS; ADJUNCTIVE TREATMENT; SEXUAL DYSFUNCTION AB Background: Psychotropic medications, particularly select antipsychotics, are a common cause of drug-induced hyperprolactinemia. As high prolactin may be associated with hypogonadism, reproductive dysfunction, and bone loss, it is important to recognize this condition and understand its management. Objective: The aim of this review is to evaluate the causes, signs, and symptoms associated with hyperprolactinemia, to describe mechanisms through which psychotropic medications elevate prolactin, and to suggest an evidence-based management approach for patients with psychotropic drug-induced hyperprolactinemia. Methods: A PubMed/MEDLINE search was conducted on the topic of psychotropic agents' as a cause of hyperprolactinemia. The material with most relevance to current psychiatric practice and of highest level of C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Dept Psychiat, Boston, MA 02114 USA. RP Nachtigall, LB (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, 0 Emerson Pl Suite 112, Boston, MA 02114 USA. EM lnachtigall@partners.org FU Cephalon/Tevia FX Dr. Jaffe has received grant funding from Cephalon/Tevia and serves in an advisory/consultant role to Noven and Sunovion. NR 43 TC 19 Z9 20 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2014 VL 55 IS 1 BP 29 EP 36 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 281SP UT WOS:000329121600003 PM 24140188 ER PT J AU Azzam, PN Gopalan, P Fricchione, GL AF Azzam, Pierre N. Gopalan, Priya Fricchione, Gregory L. TI The Early-Career Consultation Psychiatrist: The Give and Take of Mentorship SO PSYCHOSOMATICS LA English DT Letter ID ACADEMIC MEDICINE; FACULTY C1 [Azzam, Pierre N.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02115 USA. [Gopalan, Priya] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Fricchione, Gregory L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Azzam, PN (reprint author), Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02115 USA. NR 8 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2014 VL 55 IS 1 BP 105 EP 106 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 281SP UT WOS:000329121600015 PM 23932527 ER PT J AU Singh, S Kalra, MK Khawaja, RDA Padole, A Pourjabbar, S Lira, D Shepard, JAO Digumarthy, SR AF Singh, Sarabjeet Kalra, Mannudeep K. Khawaja, Ranish Deedar Ali Padole, Atul Pourjabbar, Sarvenaz Lira, Diego Shepard, Jo-Anne O. Digumarthy, Subba R. TI Radiation Dose Optimization and Thoracic Computed Tomography SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE CT radiation dose reduction; Low-dose chest CT; Dose reduction techniques; Chest CT protocol optimization ID TUBE-CURRENT MODULATION; STATISTICAL ITERATIVE RECONSTRUCTION; AUTOMATIC EXPOSURE CONTROL; CORONARY CT ANGIOGRAPHY; FILTERED BACK-PROJECTION; NOISE-REDUCTION FILTERS; HIGH-RESOLUTION CT; IMAGE-QUALITY; CHEST CT; HIGH-PITCH AB In the past 3 decades, radiation dose from computed tomography (CT) has contributed to an increase in overall radiation exposure to the population. This increase has caused concerns over harmful effects of radiation dose associated with CT in scientific publications as well as in the lay press. To address these concerns, and reduce radiation dose, several strategies to optimize radiation dose have been developed and assessed, including manual or automatic adjustment of scan parameters. This article describes conventional and contemporary techniques to reduce radiation dose associated with chest CT. C1 [Singh, Sarabjeet; Kalra, Mannudeep K.; Khawaja, Ranish Deedar Ali; Padole, Atul; Pourjabbar, Sarvenaz; Lira, Diego; Shepard, Jo-Anne O.; Digumarthy, Subba R.] Harvard Univ, Div Thorac Imaging, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Singh, S (reprint author), 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM ssingh6@partners.org NR 83 TC 9 Z9 11 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2014 VL 52 IS 1 BP 1 EP + DI 10.1016/j.rcl.2013.08.004 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 281GA UT WOS:000329086800002 PM 24267707 ER PT J AU Dichgans, M Malik, R Konig, IR Rosand, J Clarke, R Gretarsdottir, S Thorleifsson, G Mitchell, BD Assimes, TL Levi, C O'Donnell, CJ Fornage, M Thorsteinsdottir, U Psaty, BM Hengstenberg, C Seshadri, S Erdmann, J Bis, JC Peters, A Boncoraglio, GB Marz, W Meschia, JF Kathiresan, S Ikram, MA McPherson, R Stefansson, K Sudlow, C Reilly, MP Thompson, JR Sharma, P Hopewell, JC Chambers, JC Watkins, H Rothwell, PM Roberts, R Markus, HS Samani, NJ Farrall, M Schunkert, H AF Dichgans, Martin Malik, Rainer Koenig, Inke R. Rosand, Jonathan Clarke, Robert Gretarsdottir, Solveig Thorleifsson, Gudmar Mitchell, Braxton D. Assimes, Themistocles L. Levi, Christopher O'Donnell, Christopher J. Fornage, Myriam Thorsteinsdottir, Unnur Psaty, Bruce M. Hengstenberg, Christian Seshadri, Sudha Erdmann, Jeanette Bis, Joshua C. Peters, Annette Boncoraglio, Giorgio B. Maerz, Winfried Meschia, James F. Kathiresan, Sekar Ikram, M. Arfan McPherson, Ruth Stefansson, Kari Sudlow, Cathie Reilly, Muredach P. Thompson, John R. Sharma, Pankaj Hopewell, Jemma C. Chambers, John C. Watkins, Hugh Rothwell, Peter M. Roberts, Robert Markus, Hugh S. Samani, Nilesh J. Farrall, Martin Schunkert, Heribert CA METASTROKE Consortium CARDIoGRAM Consortium C4D Consortium Int Stroke Genetics Consortium TI Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease A Genome-Wide Analysis of Common Variants SO STROKE LA English DT Article DE coronary artery disease; genetics; meta-analysis; polymorphism; single nucleotide; stroke ID ASSOCIATION METAANALYSIS; ATHEROSCLEROTIC STROKE; RISK-FACTORS; LOCI; MORTALITY; PRESSURE; DESIGN AB Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Methods Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype. Results Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5x10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (P-IS=1.62x10(-7)) and ABO (P-IS=2.6x10(-4)), as well as at HDAC9 (P-LAS=2.32x10(-12)), 9p21 (P-LAS=3.70x10(-6)), RAI1-PEMT-RASD1 (P-LAS=2.69x10(-5)), EDNRA (P-LAS=7.29x10(-4)), and CYP17A1-CNNM2-NT5C2 (P-LAS=4.9x10(-4)). Conclusions Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD. C1 [Dichgans, Martin; Malik, Rainer] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Koenig, Inke R.] Univ Klinikum Schleswig Holstein, Lubeck, Germany. [Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rosand, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. [Rosand, Jonathan] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, John Radcliffe Hosp, Clin Trial Serv Unit, Oxford OX3 9DU, England. [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, John Radcliffe Hosp, Epidemiol Studies Unit, Oxford OX3 9DU, England. [Watkins, Hugh; Farrall, Martin] Univ Oxford, John Radcliffe Hosp, Wellcome Trust Ctr Human Genet, Oxford OX3 9DU, England. [Farrall, Martin] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Rothwell, Peter M.] Univ Oxford, John Radcliffe Hosp, Stroke Prevent Res Unit, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. [Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland. [Mitchell, Braxton D.] Univ Maryland Sch Med, Dept Med, Baltimore, MD USA. [Assimes, Themistocles L.] Stanford Univ Sch Med, Dept Med, Stanford, CA USA. [Levi, Christopher] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, Callaghan, NSW 2308, Australia. [Levi, Christopher] Hunter Med Res Inst, New Lambton, NSW, Australia. [O'Donnell, Christopher J.; Seshadri, Sudha] NHLBI, Bethesda, MA USA. [O'Donnell, Christopher J.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Bethesda, MA USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Hengstenberg, Christian] Klin & Poliklin Innere Med II, Regensburg, Germany. [Seshadri, Sudha] Boston Univ Sch Med, Dept Neurol, Boston, MA USA. [Erdmann, Jeanette] DZHK German Ctr Cardiovasc Res, Lubeck, Germany. [Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Boncoraglio, Giorgio B.] Ist Neurol Carlo Besta, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Dept Cerebrovasc Dis, Milan, Italy. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. [Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Roberts, Robert] Univ Ottawa Heart Inst, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Thompson, John R.] Univ Leicester, Glenfield Hosp, Dept Hlth Sci, Leicester, Leics, England. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester, Leics, England. [Sharma, Pankaj] Imperial Coll London, ICCRU, London, England. [Chambers, John C.] Imperial Coll London, Dept Epidemiol & Biostat, London, England. [Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Schunkert, Heribert] Tech Univ Munich, German Ctr Cardiovasc Res DZHK, Munich Heart Alliance, D-80290 Munich, Germany. RP Dichgans, M (reprint author), Klinikum Univ Munchen, ISD, Marchioninistr 15, Munich, Germany. EM martin.dichgans@med-uni-muenchen.de; schunkert@dhm.mhn.de RI Willenborg, Christina/D-2668-2012; Boncoraglio, Giorgio/B-8647-2011; Kessler, Thorsten/O-7426-2015; Peters, Annette/A-6117-2011; Konig, Inke/A-4544-2009; Erdmann, Jeanette/P-7513-2014; OI Willenborg, Christina/0000-0001-5217-6882; Assimes, Themistocles/0000-0003-2349-0009; Mitchell, Braxton/0000-0003-4920-4744; Seshadri, Sudha/0000-0001-6135-2622; Ikram, Mohammad Arfan/0000-0003-0372-8585; Erdmann, Jeanette/0000-0002-4486-6231; Bevan, Steve/0000-0003-0490-6830; Watkins, Hugh/0000-0002-5287-9016 FU University of Newcastle; Australian National Health and Medical Research Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G 04S 1623]; Gladys M Brawn Fellowship scheme; Vincent Fairfax Family Foundation in Australia; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN26820110 0008C, HHSN268201100009C, HHSN268201100010C, HHSN268 201100011C, HHSN268201100012C, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, N01-HC-85239, HL080295, HL087652, HL105756, R01 HL085251, R01 HL073410, HL087647, R01HL089650-02]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C]; METASTROKE project [HL-093029]; Senior Fellowship from the Department of Health (United Kingdom); National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Center for Research Resources [UL1RR033176, U54 RR020278]; National Center for Advancing Translational Sciences, Clinical and Translational Science Institute [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease [DK063491]; European Community [HEALTH-F4-2007]; FHS; National Heart, Lung, and Blood Institute's FHS [N01-HC-25195, N02-HL-6-4278]; National Institute of Neurological Disorders and Stroke [NS17950]; National Heart, Lung, and Blood Association [HL93029]; National Institute of Aging [AG033193]; NIH Genes, Environment and Health Initiative (GEI), as part of the GENEVA consortium under the NIH Genes, Environment, and Health Initiative [U01 HG004436]; Mid-Atlantic Nutrition, and Obesity Research Center [P30 DK072488]; Office of Research and Development; Medical Research Service; Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; NIH [HHSN268200782096C, Z01 AG-000015-50, N01-AG-12100, P01 HL098055, P01HL076491-06, R01DK080732, P01HL087018, 1RO1HL103931-01]; Division of Adult and Community Health; Centers for Disease Control; National Institute of Neurological Disorders and Stroke; NIH Office of Research on Women's Health [R01 NS45012, U01 NS069208-01]; UK Medical Research Council; British Heart Foundation (BHF); Merck & Co (manufacturers of simvastatin); Roche Vitamins Ltd; Merck Co.; BHF Centre of Research Excellence, Oxford [RE/08/004]; Intramural Research Program of the National Institute on Aging, NIH project [Z01 AG-000954-06]; NIH-National Institute of Neurological Disorders and Stroke [R01 NS-42733, R01 NS-39987, U01 NS069208]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010 N]; National Heart, Lung, and Blood Institute's SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic Data (STAMPEED) genomics research program [R01 HL087676]; National Center for Research Resources; Annual Research Funding of the Italian Ministry of Health [RC 2007/LR6, RC 2008/LR6, RC 2009/LR8, RC 2010/LR8]; Netherlands Organization of Scientific Research [175.010.2005.011]; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Ageing [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture, and Science; Ministry for Health, Welfare, and Sports; European Commission; Municipality of Rotterdam to the Rotterdam Study; Netherlands Heart Foundation (Nederlandse Hartstichting) [2009B102]; Wellcome Trust, as part of the WTCCC2 project [085475/B/08/Z, 085475/Z/08/Z, WT084724MA]; Medical Research Council; Stroke Association; Dunhill Medical Trust; National Institute of Health Research (NIHR); NIHR Biomedical Research Centre, Oxford; Scottish Funding Council; Chief Scientist Office; Vascular Dementia Research Foundation; BHF Center of Research Excellence in Oxford; Wellcome Trust [090532/Z/09/Z, 075491/Z/04, 084723/Z/08/Z]; Reynold's Foundation; Boehringer Ingelheim; PHILIPS medical Systems; Government of Rheinland-Pfalz in the context of the Stiftung Rheinland-Pfalz fur Innovation; research program Wissenschaft Zukunft; Johannes-Gutenberg University of Mainz in the context of the Schwerpunkt Vaskulare Pravention; MAIFOR; Fondation de France; French Ministry of Research; Institut National de la Sante et de la Recherche Medicale; Deutsche Forschungsgemeinschaft; German National Genome Research Network (NGFN-2); German National Genome Research Network (NGFN-plus); EU [LSHM-CT-2006-037593, LSHM-CT-2004-503485, HEALTHF2-2008-201668]; US NIH; National Heart, Lung, and Blood Institute's STAMPEED genomics research program [R01 HL087676]; Canada Graduate Doctoral Scholarship from the Canadian Institutes of Health Research; Cardiovascular Institute of the University of Pennsylvania; MedStar Research Institute; Washington Hospital Center; GlaxoSmithKline; GlaxoSmithKline through an Alternate Drug Discovery Initiative research alliance award; University of Pennsylvania School of Medicine; Canadian Institutes of Health Research [MOP-82810, MOP172605, MOP77682]; Canada Foundation for Innovation [11966]; Heart and Stroke Foundation of Ontario [NA6001]; BHF; Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease; National Institute on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); German Migraine & Headache Society (DMKG); Astra Zeneca; Berlin Chemie; Boots Healthcare; Glaxo-Smith-Kline; McNeil Pharma; MSD Sharp Dohme; Pfizer; Institute of Epidemiology and Social Medicine, University of Muenster; Medical Research Council (United Kingdom); Cancer Research UK; Canadian Institutes of Health Research, Heart, and Stroke Foundation of Ontario; Sanofi-Aventis; King Pharmaceuticals; LEEDS; Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development (ZonMw); Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Netherlands Organization for Scientific Research [175.010.2005.011, 911.03.012]; NGI/NWO [050-060-810]; Research Institute for Diseases in the Elderly (RIDE); NWO (Vici) [918-76-619]; Swedish Research Council; Swedish Heart & Lung Foundation; Stockholm County Council (ALF); Netherlands Heart foundation [NHS 92345]; Netherlands Organisation for Scientific Research (NWO); Italian Ministry of University and Research; Veneto Region; Cariverona Foundation, Verona; Helmholtz Zentrum Munchen-National Research Center for Environmental Health; German Federal Ministry of Education, Science, Research and Technology; State of Bavaria; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease; NIHR; European Community Sixth Framework Program [LSHM-CT-2007-037273]; AstraZeneca; Oxford BHF Centre of Research Excellence; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Torsten and Ragnar Soderberg Foundation; Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council; Foundation for Strategic Research; Stockholm County Council [560283]; National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust; National Institute for Health Research Cardiovascular Biomedical Research Unit of Royal Brompton; Harefield NHS Foundation Trust; BHF [SP/04/002]; Medical Research Council [G0601966, G0700931]; NIHR [RP-PG-0407-10371]; European Union FP7 (EpiMigrant) [279143]; Action on Hearing Loss [G51]; [R01HL087641]; [R01H L59367]; [R01HL086694]; [R01-HL087641]; [U01 HL096917]; [R01-HL093029]; [UL1RR025005]; [HHSN268201200036C] FX The Australian Stroke Genetics Collaboration (ASGC): Australian population control data were derived from the Hunter Community Study. We also thank the University of Newcastle for funding and the men and women of the Hunter region who participated in this study. This research was funded by grants from the Australian National Health and Medical Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme, and the Vincent Fairfax Family Foundation in Australia. The Atherosclerosis Risk in Communities Study (ARIC) is performed as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN26820110 0008C, HHSN268201100009C, HHSN268201100010C, HHSN268 201100011C, and HHSN268201100012C), R01HL087641, R01H L59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; National Institutes of Health (NIH) contract HHSN268200625226C; and National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, and grants R01-HL087641, U01 HL096917 (Mosley), and R01-HL093029 (Fornage). Infrastructure was partly supported by grant number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. ARIC analyses performed as part of the METASTROKE project were supported by grant HL-093029 to M. Fornage. Bio-Repository of DNA in Stroke (BRAINS) is partly funded by a Senior Fellowship from the Department of Health (United Kingdom) to Dr Sharma, the Henry Smith Charity, and the UK-India Education Research Institutive (UKIERI) from the British Council. Cardiovascular Health Study (CHS) research was supported by National Heart, Lung, and Blood Institute contracts N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, N01-HC-85239, and by HHSN268201200036C and National Heart, Lung, and Blood Institute grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping at Cedars-Sinai Medical Center were supported, in part, by the National Center for Research Resources, grant UL1RR033176, and is now at the National Center for Advancing Translational Sciences, Clinical and Translational Science Institute grant UL1TR000124, in addition to the National Institute of Diabetes and Digestive and Kidney Disease grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Genetics Work performed at deCODE was funded, in part, through a grant from the European Community's Seventh Framework Programme (FP7/2007-2013), the ENGAGE project grant agreement HEALTH-F4-2007 to 201413. The Framingham Heart Study (FHS) was supported by the dedication of the FHS participants, the National Heart, Lung, and Blood Institute's FHS (Contract Nos. N01-HC-25195 and N02-HL-6-4278) and by grants from the National Institute of Neurological Disorders and Stroke (NS17950), the National Heart, Lung, and Blood Association (HL93029), and the National Institute of Aging (AG033193).; The Genetics of Early Onset Stroke (GEOS) Study, Baltimore, was supported by the NIH Genes, Environment and Health Initiative (GEI) Grant U01 HG004436, as part of the GENEVA consortium under the NIH Genes, Environment, and Health Initiative, with additional support provided by the Mid-Atlantic Nutrition, and Obesity Research Center (P30 DK072488); and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to the Johns Hopkins University (contract number HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control, and by grants from the National Institute of Neurological Disorders and Stroke and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). Heart Protection Study (HPS; ISRCTN48489393) was supported by the UK Medical Research Council, British Heart Foundation (BHF), Merck & Co (manufacturers of simvastatin), and Roche Vitamins Ltd (manufacturers of vitamins). Genotyping was supported by a grant to Oxford University and Centre National de Genotypage from Merck & Co. Jemma C. Hopewell acknowledges support from the BHF Centre of Research Excellence, Oxford (RE/08/004). The Heart and Vascular Health Study (HVH) research reported in this article was funded by National Heart, Lung, and Blood Institute grants R01 HL085251 and R01 HL073410. The Ischemic Stroke Genetics Study (ISGS)/Siblings With Ischemic Stroke Study (SWISS) was supported, in part, by the Intramural Research Program of the National Institute on Aging, NIH project Z01 AG-000954-06. ISGS/SWISS used samples and clinical data from the NIH-National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), human subjects protocol numbers 2003-081 and 2004-147. ISGS/SWISS used stroke-free participants from the Baltimore Longitudinal Study of Aging (BLSA) as controls. The inclusion of BLSA samples was supported, in part, by the Intramural Research Program of the National Institute on Aging, NIH project Z01 AG-000015-50, human subjects protocol number 2003-078. The ISGS study was funded by NIH-National Institute of Neurological Disorders and Stroke Grant R01 NS-42733 (J.F. Meschia, P. I.). The SWISS study was funded by NIH-National Institute of Neurological Disorders and Stroke Grant R01 NS-39987 (J.F. Meschia, P. I.). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (http://biowulf.nih.gov). The MGH Genes Affecting Stroke Risk and Outcome Study (MGHGASROS) GASROS was supported by The National Institute of Neurological Disorders and Stroke (U01 NS069208), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research 0775010 N, the NIH and National Heart, Lung, and Blood Institute's SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic Data (STAMPEED) genomics research program (R01 HL087676), and a grant from the National Center for Research Resources.; The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research resources. Milano-Besta Stroke Register Collection and genotyping of the Milan cases within Cerebrovascular Diseases Registry were supported by Annual Research Funding of the Italian Ministry of Health (grant numbers: RC 2007/LR6, RC 2008/LR6, RC 2009/LR8, RC 2010/LR8). FP6 LSHM-CT-2007 to 037273 for the Precocious Coronary Artery Disease (PROCARDIS) control samples. The Rotterdam Study was supported by the Netherlands Organization of Scientific Research (175.010.2005.011), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Ageing (050-060-810), the Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture, and Science, the Ministry for Health, Welfare, and Sports, the European Commission, and the Municipality of Rotterdam to the Rotterdam Study. Further funding was obtained from the Netherlands Heart Foundation (Nederlandse Hartstichting) 2009B102. The principal funding for the Wellcome Trust Case-Control Consortium 2 (WTCCC2) stroke study was provided by the Wellcome Trust, as part of the WTCCC2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). The Stroke Association provided additional support for collection of some of the St George's, London cases. The Oxford cases were collected as part of the Oxford Vascular Study, which is funded by the Medical Research Council, Stroke Association, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Biomedical Research Centre, Oxford. The Edinburgh Stroke Study was supported by the Wellcome Trust (clinician scientist award to Dr Sudlow), and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre (www.sbirc.ed.ac.uk), Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility and part of the Scottish Imaging Network-A Platform for Scientific Excellence (SINAPSE) collaboration (www.sinapse.ac.uk), funded by the Scottish Funding Council and the Chief Scientist Office. Collection of the Munich cases and data analysis was supported by the Vascular Dementia Research Foundation. Dr Farrall acknowledges support from the BHF Center of Research Excellence in Oxford and the Wellcome Trust core award (090532/Z/09/Z). The Action in Diabetes and Vascular Disease (ADVANCE) study was supported by a grant from the Reynold's Foundation and National Heart, Lung, and Blood Institute grant HL087647. Genetic analyses of the Gutenberg Heart Study/Atherogene Study (CADomics) were supported by a research grant from Boehringer Ingelheim.; Recruitment and analysis of the CADomics cohort were supported by grants from Boehringer Ingelheim and PHILIPS medical Systems, by the Government of Rheinland-Pfalz in the context of the Stiftung Rheinland-Pfalz fur Innovation, the research program Wissenschaft Zukunft and by the Johannes-Gutenberg University of Mainz in the context of the Schwerpunkt Vaskulare Pravention and the MAIFOR grant 2001, by grants from the Fondation de France, the French Ministry of Research, and the Institut National de la Sante et de la Recherche Medicale. The deCODE CAD/MI Study was sponsored by NIH grant, National Heart, Lung, and Blood Institute R01HL089650-02. The German MI Family Studies (GerMIFS I-III [KORA]) were supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus) and the EU funded integrated project Cardiogenics (LSHM-CT-2006-037593). Ludwigshafen Risk and Cardiovascular Health (LURIC) has received funding from the EU framework 6 funded Integrated Project Bloodomics (LSHM-CT-2004-503485), the EU framework 7 funded Integrated Project AtheroRemo (HEALTHF2-2008-201668) and from Sanofi/Aventis, Roche, Dade Behring/Siemens, and AstraZeneca. The Myocardial Infarction Genetics Consortium (MIGen) study was funded by the US NIH and National Heart, Lung, and Blood Institute's STAMPEED genomics research program through R01 HL087676. Ron Do from the MIGen study is supported by a Canada Graduate Doctoral Scholarship from the Canadian Institutes of Health Research. Recruitment of PennCATH was supported by the Cardiovascular Institute of the University of Pennsylvania. Recruitment of the MedStar sample was supported, in part, by the MedStar Research Institute and the Washington Hospital Center and a research grant from GlaxoSmithKline. Genotyping of PennCATH and Medstar was performed at the Center for Applied Genomics at the Children's Hospital of Philadelphia and supported by GlaxoSmithKline through an Alternate Drug Discovery Initiative research alliance award (M. P. Reilly and D.J. Rader) with the University of Pennsylvania School of Medicine. The Ottawa Heart Genomic Study was supported by Canadian Institutes of Health Research #MOP-82810 (R. Roberts), Canada Foundation for Innovation #11966 (R. Roberts), Heart and Stroke Foundation of Ontario #NA6001 (R. McPherson), Canadian Institutes of Health Research #MOP172605 (R. McPherson), Canadian Institutes of Health Research #MOP77682 (A. F. R. Stewart). The WTCCC Study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC Study was performed by the BHF Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. N.J. Samani and S. G. Bevan hold chairs funded by the BHF. N.J. Samani and A. H. Gschwendtner are also supported by the Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease and the work described in this article is part of the research portfolio of the Leicester National Institute for Health Research Biomedical Research Unit. The Age, Gene/Environment Susceptibility Reykjavik Study has been funded by NIH contract N01-AG-12100, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The Cleveland Clinic GeneBank study was supported by NIH grants P01 HL098055, P01HL076491-06, R01DK080732, P01HL087018, and 1RO1HL103931-01.; The collection of clinical and sociodemographic data in the Dortmund Health Study was supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma (former Woelm Pharma), MSD Sharp & Dohme and Pfizer to the University of Muenster. Blood collection was done through funds from the Institute of Epidemiology and Social Medicine, University of Muenster. The EPIC-Norfolk study is supported by the Medical Research Council (United Kingdom) and Cancer Research UK. The Epidemiologic study of the determinants of diabetes, obesity and cardiovascular disease (EpiDREAM) study is supported by the Canadian Institutes of Health Research, Heart, and Stroke Foundation of Ontario, Sanofi-Aventis, GlaxoSmithKline and King Pharmaceuticals. Funding for Andrew Lotery from the LEEDS study was provided by the T. F. C. Frost charity and the Macular Disease Society. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organization for Scientific Research (NWO; 175.010.2005.011, 911.03.012), the NGI/NWO project no. 050-060-810, and Research Institute for Diseases in the Elderly (RIDE). Abbas Dehghan is supported by a grant from NWO (Vici, 918-76-619). The SAS study was funded by the BHF. The Swedish Research Council, the Swedish Heart & Lung Foundation, and the Stockholm County Council (ALF) supported the Stockholm Heart Epidemiology (SHEEP) study. Survival of Myocardial Infarction Long-term Evaluation (SMILE) was funded by the Netherlands Heart foundation (NHS 92345). Dr Rosendaal is a recipient of the Spinoza Award of the Netherlands Organisation for Scientific Research (NWO), which was used for part of this work. The Verona Heart Study was funded by grants from the Italian Ministry of University and Research, the Veneto Region, and the Cariverona Foundation, Verona. The KORA (Kooperative Gesundheitsforschung in der Region Augsburg) research platform was initiated and financed by the Helmholtz Zentrum Munchen-National Research Center for Environmental Health, which is funded by the German Federal Ministry of Education, Science, Research and Technology and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN-2 and NGFNPlus) and within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. Work described in this article is part of the research portfolio supported by the Leicester NIHR Biomedical Research Unit in Cardiovascular Disease. This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the NIHR. The Coronary Artery Disease Genetics Consortium (C4D) includes GWAS data contributed by the PROCARDIS, Life Sciences Prospective Population (LOLIPOP), and HPS studies.; PROCARDIS was supported by the European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the BHF, the Oxford BHF Centre of Research Excellence, the Wellcome Trust (075491/Z/04), the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research, and the Stockholm County Council (560283). The LOLIPOP study supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the National Institute for Health Research Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust, the BHF (SP/04/002), the Medical Research Council (G0601966, G0700931), the Wellcome Trust (084723/Z/08/Z) the NIHR (RP-PG-0407-10371), European Union FP7 (EpiMigrant, 279143), and Action on Hearing Loss (G51). We thank the participants and research staff who made the study possible. NR 31 TC 83 Z9 84 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2014 VL 45 IS 1 BP 24 EP 36 DI 10.1161/STROKEAHA.113.002707 PG 13 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 277MJ UT WOS:000328823400015 PM 24262325 ER PT J AU Nguyen, TN Malisch, T Castonguay, AC Gupta, R Sun, CHJ Martin, CO Holloway, WE Mueller-Kronast, N English, JD Linfante, I Dabus, G Marden, FA Bozorgchami, H Xavier, A Rai, AT Froehler, MT Badruddin, A Taqi, M Abraham, MG Janardhan, V Shaltoni, H Novakovic, R Yoo, AJ Abou-Chebl, A Chen, PR Britz, GW Kaushal, R Nanda, A Issa, MA Masoud, H Nogueira, RG Norbash, AM Zaidat, OO AF Nguyen, Thanh N. Malisch, Timothy Castonguay, Alicia C. Gupta, Rishi Sun, Chung-Huan J. Martin, Coleman O. Holloway, William E. Mueller-Kronast, Nils English, Joey D. Linfante, Italo Dabus, Guilherme Marden, Franklin A. Bozorgchami, Hormozd Xavier, Andrew Rai, Ansaar T. Froehler, Michael T. Badruddin, Aamir Taqi, Muhammad Abraham, Michael G. Janardhan, Vallabh Shaltoni, Hashem Novakovic, Roberta Yoo, Albert J. Abou-Chebl, Alex Chen, Peng R. Britz, Gavin W. Kaushal, Ritesh Nanda, Ashish Issa, Mohammad A. Masoud, Hesham Nogueira, Raul G. Norbash, Alexander M. Zaidat, Osama O. TI Balloon Guide Catheter Improves Revascularization and Clinical Outcomes With the Solitaire Device Analysis of the North American Solitaire Acute Stroke Registry SO STROKE LA English DT Article DE stroke; thrombectomy ID ACUTE ISCHEMIC-STROKE; FLOW-RESTORATION DEVICE; MECHANICAL THROMBECTOMY; ENDOVASCULAR TREATMENT; TRIAL; EXTRACTION; OCCLUSION; THERAPY AB Background and Purpose Efficient and timely recanalization is an important goal in acute stroke endovascular therapy. Several studies demonstrated improved recanalization and clinical outcomes with the stent retriever devices compared with the Merci device. The goal of this study was to evaluate the role of the balloon guide catheter (BGC) and recanalization success in a substudy of the North American Solitaire Acute Stroke (NASA) registry. Methods The investigator-initiated NASA registry recruited 24 clinical sites within North America to submit demographic, clinical, site-adjudicated angiographic, and clinical outcome data on consecutive patients treated with the Solitaire Flow Restoration device. BGC use was at the discretion of the treating physicians. Results There were 354 patients included in the NASA registry. BGC data were reported in 338 of 354 patients in this subanalysis, of which 149 (44%) had placement of a BGC. Mean age was 67.315.2 years, and median National Institutes of Health Stroke Scale score was 18. Patients with BGC had more hypertension (82.4% versus 72.5%; P=0.05), atrial fibrillation (50.3% versus 32.8%; P=0.001), and were more commonly administered tissue plasminogen activator (51.6% versus 38.8%; P=0.02) compared with patients without BGC. Time from symptom onset to groin puncture and number of passes were similar between the 2 groups. Procedure time was shorter in patients with BGC (120 +/- 28.5 versus 161 +/- 35.6 minutes; P=0.02), and less adjunctive therapy was used in patients with BGC (20% versus 28.6%; P=0.05). Thrombolysis in cerebral infarction 3 reperfusion scores were higher in patients with BGC (53.7% versus 32.5%; P<0.001). Distal emboli and emboli in new territory were similar between the 2 groups. Discharge National Institutes of Health Stroke Scale score (mean, 12 +/- 14.5 versus 17.5 +/- 16; P=0.002) and good clinical outcome at 3 months were superior in patients with BGC compared with patients without (51.6% versus 35.8%; P=0.02). Multivariate analysis demonstrated that the use of BGC was an independent predictor of good clinical outcome (odds ratio, 2.5; 95% confidence interval, 1.2-4.9). Conclusions Use of a BGC with the Solitaire Flow Restoration device resulted in superior revascularization results, faster procedure times, decreased need for adjunctive therapy, and improved clinical outcome. C1 [Nguyen, Thanh N.; Masoud, Hesham] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Nguyen, Thanh N.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Nguyen, Thanh N.; Masoud, Hesham; Norbash, Alexander M.] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02118 USA. [Malisch, Timothy; Marden, Franklin A.] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. [Castonguay, Alicia C.; Issa, Mohammad A.; Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Gupta, Rishi; Sun, Chung-Huan J.; Nogueira, Raul G.] Emory Univ Sch Med, Dept Neurol, Atlanta, GA USA. [Martin, Coleman O.; Holloway, William E.] St Lukes Neurosci Inst, Kansas City, MO USA. [Mueller-Kronast, Nils] Delray Med Ctr, Dept Neurol, Delray Beach, FL USA. [English, Joey D.] Calif Pacific Med Ctr, San Francisco, CA USA. [Linfante, Italo; Dabus, Guilherme] Baptist Cardiac & Vasc Inst, Div Intervent Neuroradiol, Miami, FL USA. [Bozorgchami, Hormozd] Oregon Hlth & Sci, Portland, OR USA. [Xavier, Andrew] Wayne State Univ Sch Med, Dept Neurol, Detroit, MI USA. [Rai, Ansaar T.] W Virginia Univ Hosp, Dept Radiol, Morgantown, WV USA. [Froehler, Michael T.] Vanderbilt Univ Sch Med, Dept Neurol Neurosurg & Radiol, Nashville, TN USA. [Badruddin, Aamir] Presence St Joseph Med Ctr, Dept Neurosurg, Joliet, IL USA. [Taqi, Muhammad] Desert Reg Med Ctr, Palm Springs, CA USA. [Abraham, Michael G.] Univ Kansas Med Ctr, Kansas City, MO USA. [Janardhan, Vallabh] Dallas Fort Worth Metroplex, Texas Stroke Inst, Dallas, TX USA. [Shaltoni, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Novakovic, Roberta] UT SW Med Ctr, Dept Radiol, Dallas, TX USA. [Novakovic, Roberta] UT SW Med Ctr, Dept Neurol, Dallas, TX USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. [Abou-Chebl, Alex] Univ Louisville Med Sch, Dept Neurol, Louisville, KY USA. [Chen, Peng R.] Univ Texas Houston, Houston, TX USA. [Britz, Gavin W.] Methodist Neurol Inst, Dept Neurosurg, Houston, TX USA. [Kaushal, Ritesh] Tenet Hlth Florida, Hialeah, FL USA. [Nanda, Ashish] Univ Missouri, Columbia, MO 65211 USA. RP Nguyen, TN (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 E Concord,C-3, Boston, MA 02118 USA. EM thanh.nguyen@bmc.org NR 12 TC 35 Z9 36 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2014 VL 45 IS 1 BP 141 EP 145 DI 10.1161/STROKEAHA.113.002407 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 277MJ UT WOS:000328823400033 PM 24302483 ER PT J AU Cumbler, E Wald, H Bhatt, DL Cox, M Xian, Y Reeves, M Smith, EE Schwamm, L Fonarow, GC AF Cumbler, Ethan Wald, Heidi Bhatt, Deepak L. Cox, Margueritte Xian, Ying Reeves, Mathew Smith, Eric E. Schwamm, Lee Fonarow, Gregg C. TI Quality of Care and Outcomes for In-Hospital Ischemic Stroke Findings From the National Get With The Guidelines-Stroke SO STROKE LA English DT Article DE outcome assessment (health care); quality indicators; health care; quality of health care; registries; stroke; thrombolytic therapy ID AMERICAN-HEART-ASSOCIATION; INPATIENT; IMPROVEMENT; REGISTRY; ATTACK; TIME AB Background and Purpose Analysis of quality of care for in-hospital stroke has not been previously performed at the national level. This study compares patient characteristics, process measures of quality, and outcomes for in-hospital strokes with those for community-onset strokes in a national cohort. Methods We performed a retrospective cohort study of the Get With The Guidelines-Stroke (GWTG-Stroke) database of The American Heart Association from January 2006 to April 2012, using data from 1280 sites that reported 1 in-hospital stroke. Patient characteristics, comorbid illnesses, medications, quality of care measures, and outcomes were analyzed for 21 349 in-hospital ischemic strokes compared with 928 885 community-onset ischemic strokes. Results Patients with in-hospital stroke had more thromboembolic risk factors, including atrial fibrillation, prosthetic heart valves, carotid stenosis, and heart failure (P<0.0001), and experienced more severe strokes (median National Institutes of Health Stroke Score 9.0 versus 4.0; P<0.0001). Using GWTG-Stroke achievement measures, the proportion of patients with defect-free care was lower for in-hospital strokes (60.8% versus 82.0%; P<0.0001). After accounting for patient and hospital characteristics, patients with in-hospital strokes were less likely to be discharged home (adjusted odds ratio 0.37; 95% confidence intervals [0.35-0.39]) or be able to ambulate independently at discharge (adjusted odds ratio 0.42; 95% confidence intervals [0.39-0.45]). In-hospital mortality was higher for in-hospital stroke (adjusted odds ratio 2.72; 95% confidence intervals [2.57-2.88]). Conclusions Compared with community-onset ischemic stroke, patients with in-hospital stroke experienced more severe strokes, received lower adherence to process-based quality measures, and had worse outcomes. These findings suggest there is an important opportunity for targeted quality improvement efforts for patients with in-hospital stroke. C1 [Cumbler, Ethan; Wald, Heidi] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Cox, Margueritte; Xian, Ying] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Reeves, Mathew] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Schwamm, Lee] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. RP Cumbler, E (reprint author), 12401 E 17th Ave F782, Aurora, CO 80045 USA. EM Ethan.Cumbler@ucdenver.edu OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Janssen Pharmaceutical Companies of Johnson Johnson; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; AHA Pharmaceutical Roundtable FX The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, and the AHA Pharmaceutical Roundtable. NR 26 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2014 VL 45 IS 1 BP 231 EP 238 DI 10.1161/STROKEAHA.113.003617 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 277MJ UT WOS:000328823400046 PM 24253540 ER PT J AU Sheth, KN Kimberly, WT Elm, JJ Kent, TA Mandava, P Yoo, AJ Thomalla, G Campbell, B Donnan, GA Davis, SM Albers, GW Jacobson, S Simard, JM Stern, BJ AF Sheth, Kevin N. Kimberly, W. Taylor Elm, Jordan J. Kent, Thomas A. Mandava, Pitchaiah Yoo, Albert J. Thomalla, Goetz Campbell, Bruce Donnan, Geoffrey A. Davis, Stephen M. Albers, Gregory W. Jacobson, Sven Simard, J. Marc Stern, Barney J. TI Pilot Study of Intravenous Glyburide in Patients With a Large Ischemic Stroke SO STROKE LA English DT Article DE acute treatment; brain swelling; cerebral edema; glyburide; hemorrhagic transformation; ischemic stroke ID MIDDLE CEREBRAL-ARTERY; GLIBENCLAMIDE; INFARCTION; EDEMA AB Background and Purpose Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection). Methods We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm(3), whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127 10 hours. Results Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 10223 cm(3). There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 5033 cm(3). The proportion of 90-day modified Rankin Scale 4 was 90% (40% modified Rankin Scale, 3). Conclusions RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683. C1 [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06510 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Elm, Jordan J.] Med Univ S Carolina, Dept Publ Hlth Serv, Charleston, SC USA. [Kent, Thomas A.; Mandava, Pitchaiah] Baylor Coll Med, Dept Neurol, Michael E DeBakey VA Med, Houston, TX 77030 USA. [Thomalla, Goetz] Univ Klinikum Hamburg Eppendorf, Dept Neurol, Klin & Poliklin Neurol Kopf & Neurozentrum, Hamburg, Germany. [Campbell, Bruce; Donnan, Geoffrey A.; Davis, Stephen M.] Univ Melbourne, Dept Neurol, Royal Melbourne Hosp, Melbourne Brain Ctr, Parkville, Vic, Australia. [Albers, Gregory W.] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA. [Jacobson, Sven] Remedy Pharmaceut Inc, New York, NY USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Stern, Barney J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Sheth, KN (reprint author), Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 15 York St,LCI 910A, New Haven, CT 06510 USA. EM kevin.sheth@yale.edu RI Davis, Stephen/L-5260-2013; OI Davis, Stephen/0000-0003-0962-2300; Kent, Thomas/0000-0002-9877-7584; Campbell, Bruce/0000-0003-3632-9433; Donnan, Geoffrey/0000-0001-6324-3403 FU Remedy Pharmaceuticals, Inc. FX The sponsor for this study was Remedy Pharmaceuticals, Inc. NR 9 TC 21 Z9 21 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2014 VL 45 IS 1 BP 281 EP 283 DI 10.1161/STROKEAHA.113.003352 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 277MJ UT WOS:000328823400057 PM 24193798 ER PT J AU Lo, EH AF Lo, Eng H. TI 2013 Thomas Willis Award Lecture Causation and Collaboration for Stroke Research SO STROKE LA English DT Article DE brain injuries; cerebrovascular disorders; translational research ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; MECHANISMS; BRAIN; TRANSLATION; DISEASE; REPAIR; NEUROPROTECTION; OPPORTUNITIES; MINOCYCLINE AB The pathophysiology of stroke is complex. Adaptive and maladaptive signalling occurs between multiple cell types in the brain. There is crosstalk between central and systemic responses. And there are overlapping pathways during initial injury and subsequent repair. These numerous feed-forward and feed-back interactions have made it difficult to translate experimental discoveries into clinical applications. An emerging hypothesis in biomedical research now suggests that contrary to a traditional model, translation may not be efficiently obtained without a rigorous understanding of mechanisms. Hence, to optimize diagnostics and therapeutics for stroke patients, it is necessary to identify and define causal mechanisms. Mirroring the multi-compartment interactions in stroke pathophysiology, bench-to-bedside, and bedside-back-to-bench advances in stroke may be best achieved with inter-disciplinary collaborations between basic research, neuroimaging, and broadly based clinical science. Causation can then be two-fold, ie, dissecting mechanisms and targets, as well as developing future scientists who can blur the boundaries between basic, translational, and clinical research. In systems theory, a critical goal is to distinguish causation from correlation. In stroke research, causation may perhaps be found through a collaborative search for mechanisms. C1 [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH E 149-2401,13th St, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU National Institutes of Health; American Heart Association; Rappaport Foundation FX This work supported by grants from National Institutes of Health, American Heart Association, and the Rappaport Foundation. NR 46 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2014 VL 45 IS 1 BP 305 EP 308 DI 10.1161/STROKEAHA.113.001269 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 277MJ UT WOS:000328823400063 PM 24203848 ER PT J AU Warshaw, AL Sarr, MG AF Warshaw, Andrew L. Sarr, Michael G. TI iHammer SO SURGERY LA English DT Editorial Material C1 [Warshaw, Andrew L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sarr, Michael G.] Mayo Clin, Coll Med, Dept Surg, Rochester, MN 55905 USA. RP Sarr, MG (reprint author), Mayo Clin, Coll Med, Dept Surg, 200 1st St SW,Mayo Bldg West 12, Rochester, MN 55905 USA. EM sarr.michael@mayo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2014 VL 155 IS 1 BP 201 EP 201 DI 10.1016/j.surg.2013.10.013 PG 1 WC Surgery SC Surgery GA 278TY UT WOS:000328913900027 PM 24646960 ER PT J AU Sonpavde, G Choueiri, TK AF Sonpavde, Guru Choueiri, Toni K. TI Precision medicine for metastatic renal cell carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Renal cell carcinoma; Biomarkers; Prognostic; Predictive ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-TARGETED THERAPY; SINGLE NUCLEOTIDE POLYMORPHISMS; GLOBAL EVALUATION TRIAL; CARBONIC-ANHYDRASE-IX; PHASE-III TRIAL; INTERFERON-ALPHA; CLINICAL-TRIALS; ANTIANGIOGENIC THERAPY; RETROSPECTIVE ANALYSIS AB Objectives: This review provides a broad overview of emerging data that provide hope that rational precision medicine for metastatic renal cell carcinoma (RCC) may be possible. Methods: PubMed and major conferences were searched for studies reporting potential predictive biomarkers for the therapy of metastatic RCC. Results: The availability of multiple new agents for the therapy of advanced RCC poses new challenges in terms of optimal selection of patients for the appropriate drug. Prognostic stratification based on routine histopathologic, clinical and laboratory factors have been utilized to broadly select individuals based, i.e. high-dose interleukin (IL)-2 or vascular endothelial growth factor (VEGF) inhibitors for good and intermediate risk patients and temsirolimus for poor risk patients. While multiple candidate predictive molecular biomarkers suggest that rational selection of patients for high-dose interleukin (IL)-2, and VEGF and mammalian target of rapamycin (mTOR) inhibitors may be possible, none have been validated for use in the clinic. Tumor heterogeneity and standardization of tissue collection and analysis are massive challenges that need to be addressed. Predictive molecules derived from tumor tissue, plasma and host tissue may all be predictive for therapeutic benefit. Moreover, gene expression may be modulated by multiple factors including epigenetics, transcription factors and post-transcriptional and post-translational modifications. Indeed, study of the interaction of molecular factors from all of these sources with environmental and clinical factors may be necessary to develop a unified profile composed of a panel of factors predictive of benefit from specific agents (i.e. sustained response, limited toxicity and overall a positive benefit/risk ratio). Conclusions: Conducting clinical trials with 1) prospective incorporation of promising candidate predictive molecular biomarkers, 2) novel biomarkers endpoints, and 3) mandatory biopsies of metastatic sites at different time points on therapy, are potential important steps in developing the concept of "the right medication for the right patient". (C) 2014 Elsevier Inc. All rights reserved. C1 [Sonpavde, Guru] UAB Comprehens Canc Ctr, Urol Med Oncol, Birmingham, AL USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU Novartis; Pfizer FX Gum Sonpavde, MD: Research support from Novartis, Pfizer, and speaker or advisory board for Novartis, Pfizer, and GSK. Toni K. Choueiri, MD: Research support from Pfizer. Advisory board: Pfizer, Novartis, Aveo, GSK, Bayer/Onyx, and Genentech. No speakers bureau. NR 110 TC 7 Z9 8 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 BP 5 EP 15 DI 10.1016/j.urolonc.2013.07.010 PG 11 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 281DI UT WOS:000329079700002 PM 24239472 ER PT J AU Kappel, V van Noort, B Ritschel, F Seidel, M Ehrlich, S AF Kappel, Viola van Noort, Betteke Ritschel, Franziska Seidel, Maria Ehrlich, Stefan TI Anorexia nervosa - from a neuroscience perspective SO ZEITSCHRIFT FUR KINDER-UND JUGENDPSYCHIATRIE UND PSYCHOTHERAPIE LA German DT Review DE anorexia nervosa; neurobiology; neuropsychology; endocrinology; reward system ID AGOUTI-RELATED PROTEIN; CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; EATING-DISORDERS; CENTRAL COHERENCE; DECISION-MAKING; COGNITIVE FLEXIBILITY; ENERGY-BALANCE; ADOLESCENT PATIENTS; WEIGHT RESTORATION AB Anorexia nervosa is a frequent disorder especially among adolescent girls and young women, with high morbidity, mortality, and relapse rates. To date, no single therapeutic approach has proved to be superior to others (Herpertz et al., 2011). It remains unclear how its etiology and pathology are encoded within cognitive, neural, and endocrinological processes that modulate important mechanisms in appetitive processing and weight regulation. Yet, several trait characteristics have been identified in AN which might reflect predisposing factors. Further, altered levels of neuropeptides and hormones that regulate appetite and feeding behavior have been found during both the acute and the recovered state, pointing to dysfunctional mechanisms in AN that persist even after malnutrition has ceased. Researchers are also hoping that brain imaging techniques will allow for a more detailed investigation of the neural basis of reward and punishment sensitivity that appears to be altered in AN. The integration and extension of recent findings in these areas will hopefully provide a more comprehensive understanding of the disorder and hence enable the development of more effective treatments. C1 [Kappel, Viola; van Noort, Betteke] Charite Univ Med Berlin, Klin Psychiat Psychosomat & Psychotherapie Kindes, Berlin, Germany. [Ritschel, Franziska; Seidel, Maria; Ehrlich, Stefan] Tech Univ Dresden, Univ Klinikum Gustav Carus Dresden, Klin & Poliklin Kinder & Jugendpsychiat & Psychot, Dresden, Germany. [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Sch Med,Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Ehrlich, S (reprint author), Univ Klinikum Carl Gustav Carus Dresden, Klin & Poliklin Kinder & Jugendpsychiat & Psychot, Schubertstr 42, D-01307 Dresden, Germany. EM Stefan.Ehrlich@uniklinikum-dresden.de OI Ehrlich, Stefan/0000-0003-2132-4445 NR 102 TC 2 Z9 2 U1 7 U2 31 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 1422-4917 EI 1664-2880 J9 Z KINDER JUG-PSYCH JI Z. Kinder-und Jugendpsy. Psychother. PY 2014 VL 42 IS 1 BP 39 EP 50 DI 10.1024/1422-4917/a000268 PG 12 WC Psychiatry SC Psychiatry GA 280NI UT WOS:000329036900005 PM 24365962 ER PT J AU Baek, JH Kinrys, G Nierenberg, AA AF Baek, J. H. Kinrys, G. Nierenberg, A. A. TI Lithium tremor revisited: pathophysiology and treatment SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE lithium; side-effect; bipolar disorder ID BIPOLAR DISORDER; PHYSIOLOGICAL TREMOR; MOVEMENT-DISORDERS; CENTRAL MECHANISMS; LINOLEIC-ACID; DOUBLE-BLIND; PROPRANOLOL; THERAPY; TRIAL; AMITRIPTYLINE AB ObjectiveTremor occurs frequently as a side-effect of lithium, and it is, however, easily overlooked in the clinical setting. In this article, we attempt to review the pathophysiology and the clinical approach of lithium tremor. MethodWe searched the Pubmed and Cochrane Library for relevant articles up to the year 2012. Sixty-four articles including 10 review papers, 3 clinical trials, and 12 case reports were reviewed. ResultsLithium tremor is classified as a postural tremor and subcategorized as an exaggerated physiologic tremor. Differential diagnosis includes metabolic abnormalities, benign essential tremor, Parkinson's disease, and lithium toxicity. Various methods of evaluating lithium tremor and treatment options are discussed. ConclusionWhen lithium tremor has developed, thorough history taking, physical examination, and blood examination including serum lithium level are needed. Pharmacotherapy is indicated only in patients with disabling tremor. C1 [Baek, J. H.; Kinrys, G.; Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Kinrys, G.; Nierenberg, A. A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program,Med Sch, 50 Staniford St,Ste 580, Boston, MA 02114 USA. EM anierenberg@partners.org FU NIMH; AHRQ; Forest Research Institute; PamLabs; Pfizer Pharmaceuticals, Shire; Astra Zeneca; Eli Lilly; Janssen Pharmaceuticals; Bristol-Myers Squibb; Appliance Computing, Inc.; Brain Cells, Inc.; Johnson and Johnson; Takeda/Lundbeck; Targacept; InfoMedic; Cephalon; Elan Pharmaceuticals; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithkline; Sanofi/Synthelabo; SepracorInc; Pfizer Inc; UCB Pharma; Wyeth-Ayerst Laboratories FX Dr. Nierenberg served as a consultant to American Psychiatric Association (only travel expenses paid), Appliance Computing Inc. (Mindsite), Basliea, Brain Cells, Inc., Brandeis University, Bristol Myers quibb, Corcept, Dey Pharmaceuticals, Dainippon Sumitomo, Eli Lilly and Company, EpiQ, Forest Research Institute, L.P./Mylan Inc., Novartis, PGx Health, Ridge Diganostics, Shire, Schering-Plough, Sunovian, Takeda Pharmaceuticals, Targacept; consulted for through the MGH Clinical Trials Network and Institute (CTNI), Astra Zeneca, Brain Cells, Inc, Dianippon Sumitomo/Sepracor, Johnson and Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Shire, Schering-Plough, Targacept, and Takeda/Lundbeck Pharmaceuticals. He received grant/research support through MGH from NIMH, AHRQ, Forest Research Institute, PamLabs, Pfizer Pharmaceuticals, Shire; received honoraria from Belvoir Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, CRICO, Dartmouth Medical School, IMEDEX, Israel Society for Biological Psychiatry, Johns Hopkins University, MJ Consulting, New York State, Medscape, MBL Publishing, National Association of Continuing Education, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, University of Pisa, University of Michigan, University of Miami, APSARD, ISBD, SciMed, Slack Publishing, Wolters Klower Publishing; is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Janssen Pharmaceuticals; in 2009 Astra Zeneca, Eli Lilly, and Bristol-Myers Squibb; (was) on the advisory boards of Appliance Computing, Inc., Brain Cells, Inc., Eli Lilly and Company, Johnson and Johnson, Takeda/Lundbeck, Targacept, InfoMedic; owns stock options in Appliance Computing, Inc. and Brain Cells, Inc; through MGH, Dr. Nierenberg is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Also, through MGH, Dr. Nierenberg has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression.; Dr. Kinrys served as a consultant to Astra-Zeneca, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc., UCB Pharma and Wyeth-Ayerst Laboratories; is a presenter for Astra-Zeneca, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc., UCB Pharma and Wyeth-Ayerst Laboratories; received research supports from Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Elan Pharmaceuticals, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sanofi/Synthelabo, SepracorInc., Pfizer Inc, UCB Pharma and Wyeth-Ayerst Laboratories. Dr. Kinrys reported no equity holding and no royalty/patent. Dr. Baek has no interest to disclosure. NR 60 TC 9 Z9 9 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JAN PY 2014 VL 129 IS 1 BP 17 EP 23 DI 10.1111/acps.12171 PG 7 WC Psychiatry SC Psychiatry GA 268ZM UT WOS:000328209400003 PM 23834617 ER PT J AU Kemp, DE Sylvia, LG Calabrese, JR Nierenberg, AA Thase, ME Reilly-Harrington, NA Ostacher, MJ Leon, AC Ketter, TA Friedman, ES Bowden, CL Rabideau, DJ Pencina, M Iosifescu, DV AF Kemp, D. E. Sylvia, L. G. Calabrese, J. R. Nierenberg, A. A. Thase, M. E. Reilly-Harrington, N. A. Ostacher, M. J. Leon, A. C. Ketter, T. A. Friedman, E. S. Bowden, C. L. Rabideau, D. J. Pencina, M. Iosifescu, D. V. CA LiTMUS Study Grp TI General medical burden in bipolar disorder: findings from the LiTMUS comparative effectiveness trial SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder; medical comorbidity; obesity; lithium; effectiveness ID NATIONAL EPIDEMIOLOGIC SURVEY; ILLNESS RATING-SCALE; MODERATE-DOSE-USE; I-DISORDER; METABOLIC SYNDROME; UNITED-STATES; LITHIUM-TREATMENT; PHYSICAL ILLNESS; PREVALENCE; COMORBIDITY AB ObjectiveThis study examined general medical illnesses and their association with clinical features of bipolar disorder. MethodData were cross-sectional and derived from the Lithium Treatment - Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n=264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score 4 and <4 respectively. ResultsThe baseline prevalence of significant medical comorbidity was 53% (n=139). Patients with high medical burden were more likely to present in a major depressive episode (P=.04), meet criteria for obsessive-compulsive disorder (P=.02), and experience a greater number of lifetime mood episodes (P=0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P=.002). Sixty-nine percent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI 35; 31%, n=14). ConclusionThe burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns. C1 [Kemp, D. E.; Calabrese, J. R.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Sylvia, L. G.; Nierenberg, A. A.; Reilly-Harrington, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thase, M. E.] Univ Penn, Philadelphia, PA 19104 USA. [Ostacher, M. J.; Ketter, T. A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Leon, A. C.] Weill Cornell Med Coll, New York, NY USA. [Friedman, E. S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Bowden, C. L.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Rabideau, D. J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Pencina, M.] Harvard Clin Res Inst, Boston, MA USA. [Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY USA. RP Kemp, DE (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, 10524 Euclid Ave,12th Floor, Cleveland, OH 44106 USA. EM kemp.david@gmail.com OI Ostacher, Michael/0000-0003-0353-7535 FU National Institute of Mental Health [NO1MH80001] FX Previous presentation: New Clinical Drug Evaluation Unit Annual Meeting, Phoenix, Arizona, May 29-June 1, 2012. Dedication: This work is dedicated to the memory of Andrew C. Leon, Ph.D. Funding: Study Funded by National Institute of Mental Health, Contract # NO1MH80001. NR 49 TC 28 Z9 28 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JAN PY 2014 VL 129 IS 1 BP 24 EP 34 DI 10.1111/acps.12101 PG 11 WC Psychiatry SC Psychiatry GA 268ZM UT WOS:000328209400004 PM 23465084 ER PT J AU Hser, YI Saxon, AJ Huang, D Hasson, A Thomas, C Hillhouse, M Jacobs, P Teruya, C McLaughlin, P Wiest, K Cohen, A Ling, W AF Hser, Yih-Ing Saxon, Andrew J. Huang, David Hasson, Al Thomas, Christie Hillhouse, Maureen Jacobs, Petra Teruya, Cheryl McLaughlin, Paul Wiest, Katharina Cohen, Allan Ling, Walter TI Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial SO ADDICTION LA English DT Article DE Buprenorphine; methadone; opiate dependence; treatment outcomes ID OPIOID RECEPTOR AVAILABILITY; HEROIN-DEPENDENT VOLUNTEERS; MAINTENANCE TREATMENT; ABUSE; PHARMACOLOGY; ABSTINENCE; DIVERSION; HEALTH AB AimsTo examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence. Design, settings and participantsThis secondary analysis included 1267 opioid-dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks. MeasurementsThe analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24-week trial. FindingsThe treatment completion rate was 74% for MET versus 46% for BUP (P<0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30-32mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower [odds ratio (OR)=0.63, 95% confidence interval (CI)=0.52-0.76, P<0.01] among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR)=1.61, CI=1.20-2.15], (ii) lower medication dose (<16mg for BUP, <60mg for MET; HR=3.09, CI=2.19-4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment. ConclusionsProvision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids. C1 [Hser, Yih-Ing; Huang, David; Hasson, Al; Thomas, Christie; Hillhouse, Maureen; Teruya, Cheryl; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA. [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Jacobs, Petra] Natl Inst Drug Abuse, Bethesda, MD USA. [McLaughlin, Paul] Hartford Dispensary, Hartford, CT USA. [Cohen, Allan] Bay Area Addict Res & Treatment, Hayward, CA USA. RP Hser, YI (reprint author), UCLA Integrated Substance Abuse Programs, 11075 Santa Monica Blvd,Suite 200, Los Angeles, CA 90025 USA. EM yhser@ucla.edu FU National Institute on Drug Abuse [U10 U10DA13045, K05DA017648] FX Funding was provided by the National Institute on Drug Abuse through grants U10 U10DA13045 and K05DA017648. The corresponding author, Yih-Ing Hser, has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Author contributions to the manuscript are as follows. Study concept and design: Y.-I.H., A.J.S., C.T., P.J. and W.L. Acquisition of data: A.J.S., C.T., A.H., M.H., K.W., A.C. and W.L. Analysis and interpretation of data: Y.-I.H., A.J.S., D.H., C.T., P.McL., A.C. and W.L. Drafting of the manuscript: Y.-I.H., A.J.S., D.H. and W.L. Critical revision of the manuscript for important intellectual content: Y.-I.H., A.J.S., A.H., C.T., M.H., P.J., C.T., P.McL., K.W., A.C. and W.L. Statistical analysis: D.H. and M.H. Obtaining funding: Y.-I.H., A.J.S., A.H. and W.L. Administrative, technical or material support: A.J.S., A.H., C.T., M.H. and C.T. Study supervision: Y.-I.H., A.J.S., C.T., P.J. and W.L. NR 35 TC 37 Z9 38 U1 4 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD JAN PY 2014 VL 109 IS 1 BP 79 EP 87 DI 10.1111/add.12333 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 268GD UT WOS:000328157300012 PM 23961726 ER PT J AU Durazzo, TC Mon, A Pennington, D Abe, C Gazdzinski, S Meyerhoff, DJ AF Durazzo, Timothy C. Mon, Anderson Pennington, David Abe, Christoph Gazdzinski, Stefan Meyerhoff, Dieter J. TI Interactive effects of chronic cigarette smoking and age on brain volumes in controls and alcohol-dependent individuals in early abstinence SO ADDICTION BIOLOGY LA English DT Article DE Alcohol dependence; brain reward system; brain volume; cigarette smoking; magnetic resonance imaging ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; CORTICAL THICKNESS; DRUG-USE; ALZHEIMERS-DISEASE; REWARD SYSTEM; MATTER VOLUME; USE DISORDERS; GRAY; ADDICTION AB Chronic alcohol-use disorders (AUDs) have been shown to interact with normal age-related volume loss to exacerbate brain atrophy with increasing age. However, chronic cigarette smoking, a highly co-morbid condition in AUD and its influence on age-related brain atrophy have not been evaluated. We performed 1.5T quantitative magnetic resonance imaging in non-smoking controls [non-smoking light drinking controls (nsCONs); n=54], smoking light drinking controls (sCONs, n=34), and one-week abstinent, treatment-seeking alcohol-dependent (ALC) non-smokers (nsALCs, n=35) and smokers (sALCs, n=43), to evaluate the independent and interactive effects of alcohol dependence and chronic smoking on regional cortical and subcortical brain volumes, emphasizing the brain reward/executive oversight system (BREOS). The nsCONs and sALCs showed greater age-related volume losses than the nsALCs in the dorsal prefrontal cortex (DPFC), total cortical BREOS, superior parietal lobule and putamen. The nsALCs and sALCs demonstrated smaller volumes than the nsCONs in most cortical region of interests (ROIs). The sCONs had smaller volumes than the nsCONs in the DPFC, insula, inferior parietal lobule, temporal pole/parahippocampal region and all global cortical measures. The nsALCs and sALCs had smaller volumes than the sCONs in the DPFC, superior temporal gyrus, inferior and superior parietal lobules, precuneus and all global cortical measures. Volume differences between the nsALCs and sALCs were observed only in the putamen. Alcohol consumption measures were not related to volumes in any ROI for ALC; smoking severity measures were related to corpus callosum volume in the sCONs and sALCs. The findings indicate that consideration of smoking status is necessary for a better understanding of the factors contributing to regional brain atrophy in AUD. C1 [Durazzo, Timothy C.; Mon, Anderson; Pennington, David; Abe, Christoph; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Pennington, David; Abe, Christoph; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu OI Abe, Christoph/0000-0002-1680-8480 FU National Institutes of Health [NIDA DA24136, NIAAA AA10788] FX This work was supported by the National Institutes of Health (NIDA DA24136 to TCD and NIAAA AA10788 to DJM) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. The authors have no disclosures or conflicts of interest to report. We thank Mary Rebecca Young, Kathleen Altieri, Ricky Chen and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital and Dr. David Pating, Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 52 TC 21 Z9 21 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 2014 VL 19 IS 1 BP 132 EP 143 DI 10.1111/j.1369-1600.2012.00492.x PG 12 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 274MJ UT WOS:000328610300013 PM 22943795 ER PT J AU Pusztaszeri, MP Bongiovanni, M Faquin, WC AF Pusztaszeri, Marc P. Bongiovanni, Massimo Faquin, William C. TI Update on the Cytologic and Molecular Features of Medullary Thyroid Carcinoma SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE thyroid; medullary carcinoma; fine-needle aspiration; cytology; immunocytochemistry; calcitonin; multiple endocrine neoplasia; molecular; rearranged during transfection; targeted therapy ID FINE-NEEDLE-ASPIRATION; ENDOCRINE NEOPLASIA TYPE-2; EXTRAPULMONARY SMALL-CELL; TRANSCRIPTION FACTOR-I; PHASE-II; NEUROENDOCRINE TUMORS; PROGNOSTIC-FACTORS; ECTOPIC PRODUCTION; CLINICAL-FEATURES; RET ONCOGENE AB Medullary thyroid carcinoma (MTC) accounts for only 5% to 10% of all thyroid carcinomas, but it is the most aggressive form of well-differentiated thyroid carcinoma, being responsible for 8% to 15% of all thyroid cancer-related deaths. MTC is frequently diagnosed at a locally advanced or metastatic stage, and 10-year survival rates in these cases are <20%. Fine-needle aspiration biopsy of the thyroid gland is an accurate method to diagnose MTC, having a high sensitivity and specificity. The cytologic features of MTC are characteristic and the cytologic diagnosis of classic MTC is often straightforward, especially when combined with immunocytochemistry. However, because of its morphologic heterogeneity and overlap with other tumors, the differential diagnosis of MTC on cytology and on histology is broad with several potential pitfalls. Significant advances have been made over the last decade in understanding MTC. This concerns mainly the early detection of MTC, especially in familial forms (eg, multiple endocrine neoplasia type 2), and the identification of key molecular pathways and alterations which now offer promising targets for specific therapies in progressive MTC cases. Genetic testing (eg, RET mutation) has allowed for early detection in asymptomatic carriers and high-risk patients, with prophylactic thyroidectomy often being curative. Targeted therapies with multityrosine-kinase inhibitors (eg, vandetanib or cabozantinib) have emerged as promising new treatments for recurrent or metastatic MTC. In this review article, we discuss the cytologic features of MTC and its variants, its differential diagnosis, the role of ancillary studies, and the salient molecular features of MTC. C1 [Pusztaszeri, Marc P.] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Bongiovanni, Massimo] Inst Pathol, Locarno, Switzerland. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Pusztaszeri, MP (reprint author), Hop Cantonal Univ Geneva, Serv Pathol Clin, 1 Rue Michel Servet, CH-1211 Geneva 14, Switzerland. EM marc.pusztaszeri@hcuge.ch RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 108 TC 22 Z9 25 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-4109 EI 1533-4031 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD JAN PY 2014 VL 21 IS 1 BP 26 EP 35 DI 10.1097/PAP.0000000000000004 PG 10 WC Pathology SC Pathology GA 276EO UT WOS:000328731100003 PM 24316908 ER PT J AU Mouli, VP Ananthakrishnan, AN AF Mouli, V. P. Ananthakrishnan, A. N. TI Review article: vitamin D and inflammatory bowel diseases SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID BONE-MINERAL DENSITY; RECEPTOR GENE POLYMORPHISM; TUBERCULIN SKIN-TEST; CROHNS-DISEASE; D DEFICIENCY; RISK-FACTORS; D INSUFFICIENCY; MYCOBACTERIUM-TUBERCULOSIS; 1,25-DIHYDROXYVITAMIN D-3; LATENT TUBERCULOSIS AB BackgroundVitamin D is traditionally associated with bone metabolism. The immunological effects of vitamin D have increasingly come into focus. AimTo review the evidence supporting a role of vitamin D in inflammatory bowel diseases. MethodsA comprehensive search was performed on PubMed using the terms crohn's disease' ulcerative colitis' and vitamin D'. ResultsVitamin D deficiency is common in patients with inflammatory bowel diseases (IBD) (16-95%) including those with recently diagnosed disease. Evidence supports immunological role of vitamin D in IBD. In animal models, deficiency of vitamin D increases susceptibility to dextran sodium sulphate colitis, while 1,25(OH)(2)D-3 ameliorates such colitis. One prospective cohort study found low predicted vitamin D levels to be associated with an increased risk of Crohn's disease (CD). Limited data also suggest an association between low vitamin D levels and increased disease activity, particularly in CD. In a large cohort, vitamin D deficiency (<20ng/mL) was associated with increased risk of surgery (OR 1.8, 95% CI 1.2-2.5) in CD and hospitalisations in both CD (OR 2.1, 95% CI 1.6-2.7) and UC (OR 2.3, 95% CI 1.7-3.1). A single randomised controlled trial demonstrated that vitamin D supplementation may be associated with reduced frequency of relapses in patients with CD compared with placebo (13% vs. 29%, P=0.06). ConclusionsThere is growing epidemiological evidence to suggest a role for vitamin D deficiency in the development of IBD and also its influence on disease severity. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation. C1 [Mouli, V. P.] All India Inst Med Sci, Dept Gastroenterol, New Delhi, India. [Ananthakrishnan, A. N.] Harvard Univ, Sch Med, Boston, MA USA. [Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health [K23 DK097142]; National Institutes of Health (NIH) [P30 DK043351] FX Declaration of funding interests: Dr Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). This work is also supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. NR 95 TC 62 Z9 65 U1 3 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JAN PY 2014 VL 39 IS 2 BP 125 EP 136 DI 10.1111/apt.12553 PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 269ZK UT WOS:000328283900002 PM 24236989 ER PT J AU Vergallo, R Ren, XF Yonetsu, T Kato, K Uemura, S Yu, B Jia, HB Abtahian, F Aguirre, AD Tian, JW Hu, SN Soeda, T Lee, H McNulty, I Park, SJ Jang, Y Prasad, A Lee, S Zhang, SS Porto, I Biasucci, LM Crea, F Jang, IK AF Vergallo, Rocco Ren, Xuefeng Yonetsu, Taishi Kato, Koji Uemura, Shiro Yu, Bo Jia, Haibo Abtahian, Farhad Aguirre, Aaron D. Tian, Jinwei Hu, Sining Soeda, Tsunenari Lee, Hang McNulty, Iris Park, Seung-Jung Jang, Yangsoo Prasad, Abhiram Lee, Stephen Zhang, Shaosong Porto, Italo Biasucci, Luigi M. Crea, Filippo Jang, Ik-Kyung TI Pancoronary plaque vulnerability in patients with acute coronary syndrome and ruptured culprit plaque: A 3-vessel optical coherence tomography study SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; THIN-CAP FIBROATHEROMA; INTRAVASCULAR ULTRASOUND; UNSTABLE ANGINA; LESIONS; FREQUENCY; EROSION AB Background Recent studies described different clinical and underlying plaque characteristics between patients with and without plaque rupture presenting with acute coronary syndrome (ACS). In light of the systemic nature of atherosclerosis, we hypothesized that nonculprit plaques might also express different morphological features in these 2 groups of patients. Methods Thirty-eight patients with ACS who underwent 3-vessel optical coherence tomography imaging were identified from the Massachusetts General Hospital Optical Coherence Tomography Registry. Based on culprit plaque morphology, the study population was divided into 2 groups: patients with plaque rupture at the culprit lesion (group 1) and patients with nonruptured plaque at the culprit lesion (group 2). Prevalence and features of nonculprit plaques were compared between the 2 groups. Results A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum lipid arc (198.9 degrees +/- 41.7 degrees vs 170.2 degrees +/- 41.9 degrees, P = .003), greater lipid length (7.8 +/- 4.4 mm vs 5.1 +/- 2.4 mm, P = .003), higher lipid index (1196.9 +/- 700.5 vs 747.7 +/- 377.3, P = .001), and thinner fibrous cap (107.0 +/- 56.5 mu m vs 137.3 +/- 69.8 mu m, P = .035) compared with those in group 2. Conclusions The present study showed distinctive features of nonculprit plaques between patients with ACS caused by plaque rupture and patients with ACS caused by nonruptured plaques. Patients with plaque rupture had increased pancoronary vulnerability in nonculprit plaques, suggesting that a more aggressive treatment paradigm aiming at the stabilization of vulnerable plaques may offer additional benefit to these patients. C1 [Vergallo, Rocco; Yonetsu, Taishi; Kato, Koji; Jia, Haibo; Abtahian, Farhad; Tian, Jinwei; Hu, Sining; Soeda, Tsunenari; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div, Boston, MA USA. [Ren, Xuefeng; Yu, Bo; Jia, Haibo; Tian, Jinwei; Hu, Sining] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Aguirre, Aaron D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA. [Park, Seung-Jung] Asan Med Ctr, Seoul, South Korea. [Jang, Yangsoo] Yonsei Univ, Severance Cardiovasc Hosp, Seoul 120749, South Korea. [Prasad, Abhiram] Mayo Clin, Div Cardiovasc Dis, Dept Internal Med, Rochester, MN USA. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Zhang, Shaosong] Inc St Jude Med, LightLab Imaging, Westford, MA USA. [Porto, Italo] San Donato Hosp, Cardiovasc & Neurol Dept, Arezzo, Italy. [Biasucci, Luigi M.; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, I-00168 Rome, Italy. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org OI biasucci, luigi m/0000-0002-6921-6497 FU LightLab Imaging/St Jude Medical FX Dr Jang reports receiving grant support and consulting fees from LightLab Imaging/St Jude Medical. Dr Zhang is employee of LightLab Imaging/St Jude Medical. NR 18 TC 20 Z9 22 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JAN PY 2014 VL 167 IS 1 BP 59 EP 67 DI 10.1016/j.ahj.2013.10.011 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272KG UT WOS:000328458600010 PM 24332143 ER PT J AU Rienstra, M Yin, XY Larson, MG Fontes, JD Magnani, JW McManus, DD McCabe, EL Coglianese, EE Amponsah, M Ho, JE Januzzi, JL Wollert, KC Fradley, MG Vasan, RS Ellinor, PT Wang, TJ Benjamin, EJ AF Rienstra, Michiel Yin, Xiaoyan Larson, Martin G. Fontes, Joao D. Magnani, Jared W. McManus, David D. McCabe, Elizabeth L. Coglianese, Erin E. Amponsah, Michael Ho, Jennifer E. Januzzi, James L., Jr. Wollert, Kai C. Fradley, Michael G. Vasan, Ramachandran S. Ellinor, Patrick T. Wang, Thomas J. Benjamin, Emelia J. TI Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation SO AMERICAN HEART JOURNAL LA English DT Article ID CHRONIC HEART-FAILURE; FAMILY-MEMBER ST2; RISK-FACTORS; MYOCARDIAL-INFARCTION; MULTIPLE BIOMARKERS; GENERAL-POPULATION; CARDIAC STRUCTURE; ISCHEMIC-STROKE; MORTALITY RISK; SERUM-LEVELS AB Background We investigated whether circulating concentrations of soluble ST2, growth differentiation factor-15 (GDF-5), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP). Methods We studied the relation between soluble ST2, GDF-15, and hsTnI and development of AF in Framingham Heart Study participants without prevalent AF. We used Cox proportional hazard regression analysis to examine the relation of incident AF during a 10-year follow-up period with each biomarker. We adjusted for standard AF clinical risk factors, BNP, and CRP. Results The mean age of the 3,217 participants was 59 +/- 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. In age-and sex-adjusted models, GDF-15 and hsTnI were associated with risk of incident AF; however, after including the AF risk factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777-0.830) and did not improve by adding individual or all 3 biomarkers. None of the discrimination and reclassification statistics were significant compared with the base model. Conclusion In a community-based cohort, circulating hsTnI concentrations were associated with incident AF. None of the novel biomarkers evaluated improved AF risk discrimination or reclassification beyond standard clinical AF risk factors and biomarkers. C1 [Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. [Rienstra, Michiel; Yin, Xiaoyan; Larson, Martin G.; Fontes, Joao D.; Magnani, Jared W.; Ho, Jennifer E.; Vasan, Ramachandran S.; Wang, Thomas J.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fontes, Joao D.; Magnani, Jared W.; Ho, Jennifer E.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA. [McCabe, Elizabeth L.; Coglianese, Erin E.; Januzzi, James L., Jr.; Fradley, Michael G.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div, Boston, MA USA. [Coglianese, Erin E.] Loyola Univ, Div Cardiol, Chicago, IL 60611 USA. [Amponsah, Michael] Newark Beth Israel Med Ctr, Dept Med, Newark, NJ USA. [Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. RP Rienstra, M (reprint author), Univ Groningen, Univ Med Ctr Groningen, Thoraxctr, Dept Cardiol, POB 30-001, NL-9700 RB Groningen, Netherlands. EM m.rienstra@umcg.nl OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU Roche Diagnostics; Critical Diagnostics; Singulex; BG Medicine; Siemens; Thermo-Fisher FX Dr Januzzi reports receiving grant support from Roche Diagnostics, Critical Diagnostics, Singulex, BG Medicine, Siemens, and Thermo-Fisher. NR 39 TC 20 Z9 20 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JAN PY 2014 VL 167 IS 1 BP 109 EP + DI 10.1016/j.ahj.2013.10.003 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272KG UT WOS:000328458600016 PM 24332149 ER PT J AU Akylbekova, EL Payne, JP Newton-Cheh, C May, WL Fox, ER Wilson, JG Sarpong, DF Taylor, HA Maher, JF AF Akylbekova, Ermeg L. Payne, John P. Newton-Cheh, Christopher May, Warren L. Fox, Ervin R. Wilson, James G. Sarpong, Daniel F. Taylor, Herman A. Maher, Joseph F. TI Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT interval prolongation in African Americans: The Jackson Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID SUDDEN CARDIAC DEATH; SODIUM-CHANNEL VARIANT; CHRONIC KIDNEY-DISEASE; CORRECTED QT; INFANT-DEATH; JT INTERVAL; MORTALITY; RISK; HYPERKALEMIA; ASSOCIATION AB Background African-American ancestry, hypokalemia, and QT interval prolongation on the electrocardiogram are all risk factors for sudden cardiac death (SCD), but their interactions remain to be characterized. SCN5A-1103Y is a common missense variant, of African ancestry, of the cardiac sodium channel gene. SCN5A-1103Y is known to interact with QT-prolonging factors to promote ventricular arrhythmias in persons at high risk for SCD, but its clinical impact in the general African-American population has not been established. Methods We genotyped SCN5A-S1103Y in 4,476 participants of the Jackson Heart Study, a population-based cohort of African Americans. We investigated the effect of SCN5A-1103Y, including interaction with hypokalemia, on QT interval prolongation, a widely-used indicator of prolonged myocardial repolarization and predisposition to SCD. We then evaluated the two sub-components of the QT interval: QRS duration and JT interval. Results The carrier frequency for SCN5A-1103Y was 15.4%. SCN5A-1103Y was associated with QT interval prolongation (2.7 milliseconds; P < .001) and potentiated the effect of hypokalemia on QT interval prolongation (14.6 milliseconds; P = .02). SCN5A-1103Y had opposing effects on the two sub-components of the QT interval, with shortening of QRS duration (-1.5 milliseconds; P = .001) and prolongation of the JT interval (3.4 milliseconds; P < .001). Hypokalemia was associated with diuretic use (78%; P < .001). Conclusions SCN5A-1103Y potentiates the effect of hypokalemia on prolonging myocardial repolarization in the general African-American population. These findings have clinical implications for modification of QT prolonging factors, such as hypokalemia, in the 15% of African Americans who are carriers of SCN5A-1103Y. C1 [Akylbekova, Ermeg L.; Sarpong, Daniel F.; Taylor, Herman A.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Payne, John P.] GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [May, Warren L.] Univ Mississippi, Med Ctr, Dept Biostat, Jackson, MS 39216 USA. [May, Warren L.] Univ Mississippi, Med Ctr, Dept Bioinformat, Jackson, MS 39216 USA. [Fox, Ervin R.; Wilson, James G.; Taylor, Herman A.; Maher, Joseph F.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Maher, Joseph F.] Univ Mississippi, Med Ctr, Inst Canc, Jackson, MS 39216 USA. RP Maher, JF (reprint author), Univ Mississippi, Med Ctr, Dept Med, 2500 N State St, Jackson, MS 39216 USA. EM jmaher@umc.edu FU NHLBI NIH HHS [N01HC95170, N01HC95171, N01HC95172, U01 HL065962]; NIMHD NIH HHS [P20 MD006899] NR 38 TC 3 Z9 3 U1 2 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JAN PY 2014 VL 167 IS 1 BP 116 EP + DI 10.1016/j.ahj.2013.10.009 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 272KG UT WOS:000328458600017 PM 24332150 ER PT J AU Hall, MH Levy, DL Salisbury, DF Haddad, S Gallagher, P Lohan, M Cohen, B Ongur, D Smoller, JW AF Hall, Mei-Hua Levy, Deborah L. Salisbury, Dean F. Haddad, Steve Gallagher, Patience Lohan, Mary Cohen, Bruce Oenguer, Dost Smoller, Jordan W. TI Neurophysiologic Effect of GWAS Derived Schizophrenia and Bipolar Risk Variants SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; neurophysiology; ERP; TCF4; psychosis ID DURATION MISMATCH NEGATIVITY; GENETIC-VARIATION; CONFERRING RISK; COMMON VARIANTS; BRAIN-FUNCTION; P300; PSYCHOSIS; ENDOPHENOTYPES; DISORDER; P50 AB Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) as disease associated variants for schizophrenia (SCZ), bipolar disorder (BPD), or both. Although these results are statistically robust, the functional effects of these variants and their role in the pathophysiology of SCZ or BPD remain unclear. Dissecting the effects of risk genes on distinct domains of brain function can provide important biological insights into the mechanisms by which these genes may confer illness risk. This study used quantitative event related potentials to characterize the neurophysiological effects of well-documented GWAS-derived SCZ/BPD susceptibility variants in order to map gene effects onto important domains of brain function. We genotyped 199 patients with DSM-IV diagnoses of SCZ or BPD and 74 healthy control subjects for 19 risk SNPs derived from previous GWAS findings and tested their association with five neurophysiologic traits (P3 amplitude, P3 latency, N1 amplitude, P2 amplitude, and P50 sensory gating responses) known to be abnormal in psychosis. The TCF4 SNP rs17512836 risk allele showed a significant association with reduced auditory P3 amplitude (P=0.00016) after correction for multiple testing. The same allele was also associated with delayed P3 latency (P=0.005). Our results suggest that a SCZ risk variant in TCF4 is associated with neurophysiologic traits thought to index attention and working memory abnormalities in psychotic disorders. These findings suggest a mechanism by which TCF4 may contribute to the neurobiological basis of psychotic illness. (c) 2013 Wiley Periodicals, Inc. C1 [Hall, Mei-Hua; Oenguer, Dost] Harvard Univ, McLean Hosp, Sch Med, Psychot Disorders Div,Dept Psychiat, Belmont, MA 02478 USA. [Hall, Mei-Hua; Levy, Deborah L.; Lohan, Mary] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat,Psychol Res Lab, Belmont, MA 02478 USA. [Hall, Mei-Hua; Haddad, Steve; Gallagher, Patience; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Salisbury, Dean F.] Univ Pittsburgh, Sch Med, Clin Neurophysiol Res Lab, Pittsburgh, PA USA. [Cohen, Bruce] Harvard Univ, McLean Hosp, Sch Med, Shervert Frazier Res Inst, Belmont, MA 02478 USA. RP Hall, MH (reprint author), Harvard Univ, McLean Hosp, Sch Med, Psychol Res Lab, 115 Mill St, Belmont, MA 02478 USA. EM mhall@mclean.harvard.edu FU National Institute of Mental Health [1K01MH086714, K24MH094614]; Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources); National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05]; Harvard University and its affiliated academic health care centers FX Grant sponsor: National Institute of Mental Health; Grant numbers: 1K01MH086714, K24MH094614; Grant sponsor: This work was conducted with support from Harvard Catalyst. The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers. NR 50 TC 11 Z9 11 U1 5 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2014 VL 165 IS 1 BP 9 EP 18 DI 10.1002/ajmg.b.32212 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 272IQ UT WOS:000328454100002 PM 24339136 ER PT J AU Haspot, F Li, HW Lucas, CL Fehr, T Beyaz, S Sykes, M AF Haspot, F. Li, H. W. Lucas, C. L. Fehr, T. Beyaz, S. Sykes, M. TI Allospecific Rejection of MHC Class I-Deficient Bone Marrow by CD8 T Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; CD8 T cells; indirect alloreactivity; tolerance ID TUMOR-NECROSIS-FACTOR; CD40-CD40 LIGAND INTERACTIONS; MEDIATED ALLORESISTANCE; TRANSPLANTATION; TOLERANCE; MICE; RECEPTORS; VIVO; INDUCTION; PATHWAY AB Avoidance of long-term immunosuppression is a desired goal in organ transplantation. Mixed chimerism offers a promising approach to tolerance induction, and we have aimed to develop low-toxicity, nonimmunodepleting approaches to achieve this outcome. In a mouse model achieving fully MHC-mismatched allogeneic bone marrow engraftment with minimal conditioning (3Gy total body irradiation followed by anti-CD154 and T cell-depleted allogeneic bone marrow cells), CD4 T cells in the recipient are required to promote tolerance of preexisting alloreactive recipient CD8 T cells and thereby permit chimerism induction. We now demonstrate that mice devoid of CD4 T cells and NK cells reject MHC Class I-deficient and Class I/Class II-deficient marrow in a CD8 T cell-dependent manner. This rejection is specific for donor alloantigens, since recipient hematopoiesis is not affected by donor marrow rejection and MHC Class I-deficient bone marrow that is syngeneic to the recipient is not rejected. Recipient CD8 T cells are activated and develop cytotoxicity against MHC Class I-deficient donor cells in association with rejection. These data implicate a novel CD8 T cell-dependent bone marrow rejection pathway, wherein recipient CD8 T cells indirectly activated by donor alloantigens promote direct killing, in a T cell receptor-independent manner, of Class I-deficient donor cells. In a nonmyeloablative mouse bone marrow transplant model, the authors observe that recipient CD8 T cells specifically reject allogeneic, but not syngeneic, marrow lacking MHC class I heavy or light chains, in a manner that implicates indirect allorecognition through a TCR-independent recognition pathway. C1 [Haspot, F.; Li, H. W.; Lucas, C. L.; Fehr, T.; Beyaz, S.; Sykes, M.] Harvard Univ, Sch Med, Dept Med, Transplantat Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, H. W.; Sykes, M.] Columbia Univ, Coll Phys & Surg, Dept Med, Columbia Ctr Translat Immunol, New York, NY USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Dept Med, Transplantat Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM megan.sykes@columbia.edu OI Beyaz, Semir/0000-0003-4730-4012 FU National Institutes of Health [R01 HL49915, P01 HL18646]; Fondation pour la Recherche Medicale (France); American Society of Transplantation/American Society of Blood and Marrow Transplantation (USA); Swiss Foundation for Medical and Biological Grants/Novartis Switzerland; Walter and Gertrud Siegenthaler Foundation (University of Zurich); DoD; Air Force Office of Scientific Research; National Defense Science and Engineering Graduate (NDSEG) Fellowship [32 CFR 168a] FX We thank Ms. Shavree Washington for expert assistance with the manuscript and Drs. Donna Farber, Gilles Benichou and Josef Kurtz for helpful comments on the paper. This work was supported by National Institutes of Health Grants R01 HL49915 and P01 HL18646. FH was supported by the Fondation pour la Recherche Medicale (France), and the American Society of Transplantation/American Society of Blood and Marrow Transplantation (USA). TF was supported by the Swiss Foundation for Medical and Biological Grants/Novartis Switzerland and the Walter and Gertrud Siegenthaler Foundation (University of Zurich). CLL was supported by government funds awarded by DoD, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEG) Fellowship, 32 CFR 168a. NR 35 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 IS 1 BP 49 EP 58 DI 10.1111/ajt.12525 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 274HR UT WOS:000328597900009 PM 24304495 ER PT J AU Elias, N Cosimi, AB Hertl, M AF Elias, N. Cosimi, A. B. Hertl, M. TI Auxiliary Liver Transplant Is an Effective and Safe Treatment of Primary Hyperoxaluria SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Letter ID GLYCOLATE C1 [Elias, N.; Cosimi, A. B.; Hertl, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Elias, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Elias.Nahel@MGH.Harvard.edu NR 7 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2014 VL 14 IS 1 BP 242 EP 242 DI 10.1111/ajt.12534 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 274HR UT WOS:000328597900036 PM 24299026 ER PT J AU Guenechea-Sola, M Hariri, SR Galoosian, A Yusin, JS AF Guenechea-Sola, Miren Hariri, Sherwin R. Galoosian, Artin Yusin, Joseph S. TI A retrospective review of veterans' adherence to allergen immunotherapy over 10 years SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter C1 [Guenechea-Sola, Miren] Cedars Sinai Med Ctr, Dept Internal Med, Los Angeles, CA 90048 USA. [Hariri, Sherwin R.; Galoosian, Artin; Yusin, Joseph S.] W Los Angeles Vet Affairs Med Ctr, Dept Allergy Immunol, Los Angeles, CA 90073 USA. [Galoosian, Artin] George Washington Univ, Sch Med, Washington, DC USA. RP Guenechea-Sola, M (reprint author), Cedars Sinai Med Ctr, Dept Internal Med, Los Angeles, CA 90048 USA. EM miren.guenechea-sola@cshs.org NR 7 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JAN PY 2014 VL 112 IS 1 BP 79 EP 81 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 274ZF UT WOS:000328644000023 PM 24331403 ER PT J AU Barshes, NR Kougias, P Ozaki, CK Pisimisis, G Bechara, CF Henson, HK Belkin, M AF Barshes, Neal R. Kougias, Panos Ozaki, C. Keith Pisimisis, George Bechara, Carlos F. Henson, Helene K. Belkin, Michael TI Cost-effectiveness of Revascularization for Limb Preservation in Patients with Marginal Functional Status SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Winter Meeting of the Peripheral-Vascular-Surgery-Society CY JAN 31-FEB 03, 2013 CL Park City, UT SP Peripheral Vasc Surg Soc ID INFRAINGUINAL ARTERIAL RECONSTRUCTION; LOWER-EXTREMITY BYPASS; CONTEMPORARY MANAGEMENT; ISCHEMIA; SALVAGE; OCTOGENARIANS; AMPUTATION; DISEASE; TRIAL; GRAFT AB Background: Revascularization and limb salvage attempts are often offered to patients with foot wounds and chronic limb ischemia who are thought to be good-risk candidates, but some skepticism remains about the utility of these efforts for elderly patients with marginal functional status. We sought to determine whether limb preservation efforts in this population could be justified from a patient-centered, cost-effectiveness perspective. Methods: A probabilistic Markov model was used to simulate the clinical outcomes, health utilities, and costs over a 10-year period with various management strategies. Clinical parameter estimates were obtained from previous clinical trials and large observational series. Cost estimates were obtained from cost literature and also a single-center study that reviewed total costs accumulated (including secondary amputations, wound care, outpatient nursing care, and nursing home costs). Cost (in 2011 U. S. dollars) per year of ambulation (with limb preservation or with a prosthesis after amputation) was the primary measure of cost-effectiveness. Results: The total 10-year costs of revascularization-either endovascular or surgical-were lower than the costs of either local wound care alone or primary amputation. Revascularization strategies also produced more health benefits as measured in terms of years of ambulatory ability, years of limb salvage, or quality-adjusted life-years. In none of the scenarios modeled in deterministic sensitivity analyses did primary amputation prove to be cost-effective. Conclusions: Revascularization and limb preservation attempts appear less costly and provide more health benefits than wound care alone or primary amputation, even among patients with marginal functional status at baseline. C1 [Barshes, Neal R.; Kougias, Panos; Pisimisis, George; Bechara, Carlos F.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. [Ozaki, C. Keith; Belkin, Michael] Brigham & Womens Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Henson, Helene K.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Phys Med & Rehabil, Houston, TX 77030 USA. RP Barshes, NR (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc & Endovasc Surg, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. EM nbarshes@bcm.edu NR 22 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JAN PY 2014 VL 28 IS 1 BP 10 EP 17 DI 10.1016/j.avsg.2013.08.004 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 275AD UT WOS:000328646400002 PM 24332257 ER PT J AU Barshes, NR Bechara, CF Pisimisis, G Kougias, P AF Barshes, Neal R. Bechara, Carlos F. Pisimisis, George Kougias, Panos TI Preliminary Experiences with Early Primary Closure of Foot Wounds after Lower Extremity Revascularization SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Winter Meeting of the Peripheral-Vascular-Surgery-Society CY JAN 31-FEB 03, 2013 CL Park City, UT SP Peripheral Vasc Surg Soc ID CRITICAL LIMB ISCHEMIA; INFRAINGUINAL BYPASS; COST-EFFECTIVENESS; AMPUTATION; OUTCOMES; SURGERY; PREVENTION; MANAGEMENT; TRIAL; GRAFT AB Background: The costs associated with local wound care after revascularization can be significant, and it has been suggested that early closure or healing of foot wounds can be a source of cost savings. We sought to determine the safety and effectiveness of attempts to primarily close chronic foot wounds early after revascularization. Methods: We performed a single-center 1-year review of patients who underwent primary wound closure during the same hospitalization as revascularization. Results: Seven patients underwent an attempt at early primary wound closure. Most (71%) were diabetic. The wounds were primarily closed at a median of 6 days after revascularization (range 3-8 days). The limb-salvage rate at 6 months was 86%. Four patients remained completely healed with primary closure. One healed secondarily with wound care, and 2 required major amputation. Wound-closure techniques included the use of toe/forefoot amputations, skin grafting, and local flaps. Conclusions: Early primary closure after revascularization may be a safe technique to consider for carefully selected foot wounds without ongoing soft tissue infection. C1 [Barshes, Neal R.; Bechara, Carlos F.; Pisimisis, George; Kougias, Panos] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Surg, Houston, TX 77030 USA. RP Barshes, NR (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Div Vasc & Endovasc Surg, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. EM nbarshes@bcm.tmc.edu NR 18 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JAN PY 2014 VL 28 IS 1 BP 48 EP 52 DI 10.1016/j.avsg.2013.06.012 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 275AD UT WOS:000328646400006 PM 24189006 ER PT J AU Leutwyler, H Hubbard, EM Jeste, DV Miller, B Vinogradov, S AF Leutwyler, Heather Hubbard, Erin M. Jeste, Dilip V. Miller, Bruce Vinogradov, Sophia TI Associations of Schizophrenia Symptoms and Neurocognition With Physical Activity in Older Adults With Schizophrenia SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE schizophrenia; physical activity; symptomatology; neurocognition ID MEDICAL COMORBIDITY; FUNCTIONAL STATUS; MENTAL-ILLNESS; HEALTH; TRIAL; PANSS AB Background: Low levels of physical activity contribute to the generally poor physical health of older adults with schizophrenia. The associations linking schizophrenia symptoms, neurocognition, and physical activity are not known. Research is needed to identify the reasons for this population's lack of adequate physical activity before appropriate interventions can be designed and tested. Design and Methods: In this cross-sectional study, 30 adults aged 55 years with schizophrenia were assessed on symptoms (Positive and Negative Syndrome Scale), neurocognition (MATRICS Consensus Cognitive Battery), and physical activity (Sensewear ProArmband). Pearson's bivariate correlations (two-tailed) and univariate linear regression models were used to test the following hypotheses: (1) more severe schizophrenia symptoms are associated with lower levels of physical activity and (2) more severe neurocognitive deficits are associated with lower levels of physical activity. Results: Higher scores on a speed-of-processing test were associated with more average daily steps (p = .002) and more average daily minutes of moderate physical activity (p = .009). Higher scores on a verbal working memory task were associated with more average daily minutes of moderate physical activity (p = .05). More severe depressive symptoms were associated with more average daily minutes of sedentary activity (p = .03). Conclusion: Physical activity interventions for this population are imperative. In order for a physical activity intervention to be successful, it must include components to enhance cognition and diminish psychiatric symptoms. C1 [Leutwyler, Heather; Hubbard, Erin M.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Jeste, Dilip V.] Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, Dept Psychiat & Neurosci, San Diego, CA 92103 USA. [Miller, Bruce] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. RP Leutwyler, H (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, 2 Koret Way,N631A,Box 0610, San Francisco, CA 94143 USA. EM heather.leutwyler@nursing.ucsf.edu FU UCSF Academic Senate; National Center for Research Resources [KL2R024130, UCSF-CTSI UL1 RR024131]; National Institute of Nursing Research [P30-NR011934-0] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the UCSF Academic Senate (Individual Investigator Grant), National Center for Research Resources (KL2R024130 to H. L. & UCSF-CTSI UL1 RR024131), and the National Institute of Nursing Research (P30-NR011934-0). NR 33 TC 14 Z9 14 U1 3 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 EI 1552-4175 J9 BIOL RES NURS JI Biol. Res. Nurs. PD JAN PY 2014 VL 16 IS 1 BP 23 EP 30 DI 10.1177/1099800413500845 PG 8 WC Nursing SC Nursing GA 274CE UT WOS:000328581900004 PM 24057223 ER PT J AU Sherry, D Knight, BP Casey, C Larson, J Hacker, ED Quinn, LT Wang, E Collins, EG AF Sherry, Daisy Knight, Bradley P. Casey, Cash Larson, Janet Hacker, Eileen D. Quinn, Lauretta T. Wang, Edward Collins, Eileen G. TI A Pilot Study Evaluating Daily Physical Activity Before and After Cardiac Resynchronization Therapy SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE cardiac resynchronization therapy; physical activity; heart failure ID CHRONIC HEART-FAILURE; QUESTIONNAIRE CHINESE VERSION; RANDOMIZED CONTROLLED-TRIAL; VALIDATION AB Benefits of daily physical activity are well known, but there are limited data to describe physical activity in heart failure patients who receive cardiac resynchronization therapy devices. The purpose of this pilot study was to evaluate changes in physical activity (PA) levels before and 3 months after Cardiac Resynchronization Therapy (CRT) and determine relationships of PA to physical function and comorbidities, as well as describe changes in heart failure symptoms. This was a prospective pre-/post- design that included a convenience sample of 21 subjects using self- report questionnaires and 6-minute walk test (6MWT). In this sample, there was a 2.6 hour increase in high level PA (p = 0.024). 6MW distance improved 27% (p < .0001). Subjects experienced a 25% reduction in dyspnea (p = 0.015). Knowledge gained from this study adds to the understanding of the patient response to CRT. Further study is recommended to generalize findings and explore whether an intervention (cardiac rehabilitation) is indicated. C1 [Sherry, Daisy] US Dept Vet Affairs, Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [Knight, Bradley P.] NW Mem Hosp, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. [Casey, Cash] Midwest Heart Specialists, Elmhurst, IL USA. [Larson, Janet; Hacker, Eileen D.; Quinn, Lauretta T.; Wang, Edward; Collins, Eileen G.] Univ Illinois, Coll Nursing, Dept Biobehav Hlth Sci, Chicago, IL USA. [Larson, Janet] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Collins, Eileen G.] Edward Hines Jr VA Hosp, Dept Rehabil, Hines, IL USA. RP Sherry, D (reprint author), US Dept Vet Affairs, Edward Hines Jr VA Hosp, 5000 S 5th Ave, Hines, IL 60141 USA. EM daisyc6@juno.com FU National Institute of Nursing Research's Ruth L. Kirchstein National Research Service Award [5F31NR009901] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr. Sherry received funding for this study through the National Institute of Nursing Research's Ruth L. Kirchstein National Research Service Award, #5F31NR009901. NR 22 TC 0 Z9 0 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 EI 1552-4175 J9 BIOL RES NURS JI Biol. Res. Nurs. PD JAN PY 2014 VL 16 IS 1 BP 31 EP 37 DI 10.1177/1099800413481619 PG 7 WC Nursing SC Nursing GA 274CE UT WOS:000328581900005 PM 23539670 ER PT J AU Schoenfeld, AR Al-Damluji, MS Horwitz, LI AF Schoenfeld, Amy R. Al-Damluji, Mohammed Salim Horwitz, Leora I. TI Sign-out snapshot: cross-sectional evaluation of written sign-outs among specialties SO BMJ QUALITY & SAFETY LA English DT Article ID PATIENT-CARE; COMMUNICATION FAILURES; HOUSE STAFF; IMPROVEMENT; CURRICULUM; HANDOFFS; HANDOVER; INTERNS AB Background Sign-out is the process (written, verbal or both) by which one clinical team transmits information about patients to another team. Poor quality sign-outs are associated with adverse events and delayed treatment. How different specialties approach written sign-outs is unknown. Objective To compare written sign-out practices across specialties and to determine consistency of content, format and timeliness. Methods The authors evaluated all non-Intensive Care Unit written sign-outs from five inpatient specialties on 18 January 2012, at Yale-New Haven Hospital, focusing on content elements, format style and whether the sign-outs had been updated within 24h. In our institution, all specialties used a single standardised sign-out template, which was built into the electronic medical record. Results The final cohort included 457 sign-outs: 313 medicine, 64 general surgery, 36 paediatrics, 30 obstetrics, and 14 gynaecology. Though nearly all sign-outs (96%) had been updated within 24h, they frequently lacked key information. Hospital course prevalence ranged from 57% (gynaecology) to 100% (paediatrics) (p<0.001). Clinical condition prevalence ranged from 34% (surgery) to 72% (paediatrics) (p=0.005). Conclusions Specialties have varied sign-out practices, and thus structured templates alone do not guarantee inclusion of critical content. Sign-outs across specialties often lacked complex clinical information such as clinical condition, anticipatory guidance and overnight tasks. C1 [Schoenfeld, Amy R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Al-Damluji, Mohammed Salim; Horwitz, Leora I.] Yale Univ, Sch Med, Dept Med, Sect Gen Internal Med, New Haven, CT 06520 USA. [Horwitz, Leora I.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Horwitz, LI (reprint author), Yale Univ, Sch Med, Dept Gen Internal Med, POB 208093,367 Cedar St, New Haven, CT 06520 USA. EM leora.horwitz@yale.edu OI Horwitz, Leora/0000-0003-1800-6040 FU National Institute on Aging [K08 AG038336]; American Federation for Aging Research through the Paul B Beeson Career Development Award Program; Claude D Pepper Older Americans Independence Center at Yale University School of Medicine [P30AG021342 NIH/NIA]; Yale School of Medicine Office of Student Research FX LIH is supported by the National Institute on Aging (K08 AG038336) and by the American Federation for Aging Research through the Paul B Beeson Career Development Award Program. LIH is also a Pepper Scholar with support from the Claude D Pepper Older Americans Independence Center at Yale University School of Medicine (#P30AG021342 NIH/NIA). This project was also supported by the Yale School of Medicine Office of Student Research. NR 21 TC 5 Z9 5 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JAN PY 2014 VL 23 IS 1 BP 66 EP 72 DI 10.1136/bmjqs-2013-002164 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 270BR UT WOS:000328292600009 PM 23996093 ER PT J AU Slopen, N McLaughlin, KA Dunn, EC Koenen, KC AF Slopen, Natalie McLaughlin, Katie A. Dunn, Erin C. Koenen, Karestan C. TI Childhood adversity and cell-mediated immunity in young adulthood: Does type and timing matter? (vol 28, pg 63, 2013) SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Correction C1 [Slopen, Natalie] Ctr Developing Child, Cambridge, MA 02138 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. RP Slopen, N (reprint author), Harvard Univ, Ctr Developing Child, 50 Church St,4th Floor, Cambridge, MA 02138 USA. EM nslopen@hsph.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2014 VL 35 BP 191 EP 192 DI 10.1016/j.bbi.2013.07.178 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 274EJ UT WOS:000328588400023 ER PT J AU Stein, TD Chae, YS Won, N Lee, JH Hedley-Whyte, ET AF Stein, Thor D. Chae, Yang-seok Won, Namehee Lee, Jeong-hyun Hedley-Whyte, E. Tessa TI A 34-YEAR-OLD MAN WITH BITEMPORAL HEMIANOPSIA SO BRAIN PATHOLOGY LA English DT Editorial Material ID INTRASELLAR RHABDOMYOSARCOMA C1 [Stein, Thor D.; Hedley-Whyte, E. Tessa] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Chae, Yang-seok; Won, Namehee; Lee, Jeong-hyun] Korea Univ, Anam Hosp, Seoul, South Korea. RP Stein, TD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. OI Stein, Thor/0000-0001-6954-4477 FU CSRD VA [I01 CX001038] NR 3 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2014 VL 24 IS 1 BP 107 EP 110 DI 10.1111/bpa.12108 PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 274PQ UT WOS:000328618900013 PM 24345226 ER PT J AU Abdelmalak, BB Knittel, J Abdelmalak, JB Dalton, JE Christiansen, E Foss, J Argalious, M Zimmerman, R Van den Berghe, G AF Abdelmalak, B. B. Knittel, J. Abdelmalak, J. B. Dalton, J. E. Christiansen, E. Foss, J. Argalious, M. Zimmerman, R. Van den Berghe, G. TI Preoperative blood glucose concentrations and postoperative outcomes after elective non-cardiac surgery: an observational study SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthesia; general; diabetes mellitus; general surgery; hyperglycaemia; mortality ID RANDOMIZED CONTROLLED-TRIAL; INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; C-REACTIVE PROTEIN; HOSPITALIZED-PATIENTS; QUANTILE REGRESSION; DIABETES-MELLITUS; LIGHT ANESTHESIA; CRITICAL ILLNESS; DEXAMETHASONE AB The association between preoperative blood glucose (BG) concentration and outcomes after non-cardiac surgery and the impact of the diabetes diagnosis status remain unclear. We tested two hypotheses: that preoperative BG is related to surgical outcomes; and that this relationship depends on the diabetes diagnosis status of the patient. We retrospectively analysed data on 61 536 consecutive elective non-cardiac surgery patients treated at our tertiary care facility. Logistic regression models were used to test the hypotheses before and after adjustment for baseline patient characteristics. Our primary outcome was a composite of in-hospital serious complications and mortality. A second primary outcome was 1 yr mortality. The crude incidence of the composite in-hospital outcome was significantly related to preoperative BG (P0.001), but not after covariable adjustment (P0.40). This relationship did not significantly differ between patients with and without diagnosed diabetes (P0.09). One year mortality was significantly related to preoperative BG, both univariably (P0.001) and after covariable-adjustment (P0.001). Patients with diagnosed diabetes and preoperative euglycaemia generally had worse 1 yr mortality than those without diabetes at the same BG {e.g. odds ratio (OR) [95 confidence interval (CI)] of 1.27 (1.06, 1.53) at 6 mmol litre(1) (108 mg dl(1)), P0.003}. Conversely, hyperglycaemic patients with diagnosed diabetes displayed a significantly lower 1 yr mortality than hyperglycaemic patients without diabetes [OR (95 CI) of 0.58 (0.44, 0.77) at 12 mmol litre(1) (216 mg dl(1)), P0.001]. For elective non-cardiac surgery, preoperative hyperglycaemia should be given greater consideration in patients without diabetes than in those with diagnosed diabetes. C1 [Abdelmalak, B. B.; Foss, J.; Argalious, M.] Cleveland Clin, Dept Gen Anesthesiol, Inst Anesthesiol, Cleveland, OH 44195 USA. [Abdelmalak, B. B.; Dalton, J. E.] Cleveland Clin, Dept Outcomes Res, Inst Anesthesiol, Cleveland, OH 44195 USA. [Knittel, J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, Boston, MA 02114 USA. [Abdelmalak, J. B.; Christiansen, E.] Cleveland Clin, Inst Anesthesiol, Cleveland, OH 44195 USA. [Dalton, J. E.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Zimmerman, R.] Cleveland Clin, Inst Med, Dept Endocrinol, Cleveland, OH 44195 USA. [Van den Berghe, G.] Catholic Univ Louvain, B-3000 Louvain, Belgium. RP Abdelmalak, BB (reprint author), Cleveland Clin, Gen Anesthesiol E31,9500 Euclid Ave, Cleveland, OH 44195 USA. EM abdelmb@ccf.org NR 32 TC 9 Z9 10 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 EI 1471-6771 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JAN PY 2014 VL 112 IS 1 BP 79 EP 88 DI 10.1093/bja/aet297 PG 10 WC Anesthesiology SC Anesthesiology GA 271PS UT WOS:000328404700013 PM 24009267 ER PT J AU Ruddy, KJ Gelber, S Tamimi, RM Schapira, L Come, SE Meyer, ME Winer, EP Partridge, AH AF Ruddy, Kathryn J. Gelber, Shari Tamimi, Rulla M. Schapira, Lidia Come, Steven E. Meyer, Meghan E. Winer, Eric P. Partridge, Ann H. TI Breast Cancer Presentation and Diagnostic Delays in Young Women SO CANCER LA English DT Article DE breast neoplasms; early detection of cancer; breast self-examination; neoplasm metastasis; psychosocial factors ID SURVIVAL; FEATURES; AGE; DISEASE; STAGE AB BACKGROUNDYoung women may experience delays in diagnosis of breast cancer, and these delays may contribute to poorer outcomes. METHODSIn a prospective, multicenter cohort study, women recently diagnosed with breast cancer at age 40 years were surveyed regarding their initial signs or symptoms of cancer and delays in diagnosis. Self delay was defined as 90 days between the first sign or symptom and a patient's first visit to consult a health care provider. Care delay was defined as 90 days between that first visit and the diagnosis of breast cancer. In a medical record review, tumor characteristics were assessed, including disease stage. Univariate and multivariate models were used to assess for predictors of self delay, care delay, and advanced stage in the self-detected subset. RESULTSIn 585 eligible participants, the first sign or symptom of cancer was a self-detected breast abnormality for 80%, a clinical breast examination abnormality for 6%, an imaging abnormality for 12%, and a systemic symptom for 1%. Among women with self-detected cancers, 17% reported a self delay, and 12% reported a care delay. Self delays were associated with poorer financial status (P=0.01). Among young women with self-detected breast cancers, care delay was associated at trend level (P=.06) with higher stage in multivariate modeling. CONCLUSIONSMost young women detect their own breast cancers, and most do not experience long delays before diagnosis. Women with fewer financial resources are more likely to delay seeking medical attention for a self-detected breast abnormality. Cancer 2014;120:20-25. (c) 2013 American Cancer Society. C1 [Ruddy, Kathryn J.; Gelber, Shari; Meyer, Meghan E.; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Tamimi, Rulla M.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Come, Steven E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM katieruddy@gmail.com FU Susan G. Komen for the Cure FX This study was supported by a grant from Susan G. Komen for the Cure (Ann H. Partridge, principal investigator). NR 14 TC 11 Z9 11 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2014 VL 120 IS 1 BP 20 EP 25 DI 10.1002/cncr.28287 PG 6 WC Oncology SC Oncology GA 272EL UT WOS:000328443000007 PM 24347383 ER PT J AU Sethi, RV Shih, HA Yeap, BY Mouw, KW Petersen, R Kim, DY Munzenrider, JE Grabowski, E Rodriguez-Galindo, C Yock, TI Tarbell, NJ Marcus, KJ Mukai, S MacDonald, SM AF Sethi, Roshan V. Shih, Helen A. Yeap, Beow Y. Mouw, Kent W. Petersen, Robert Kim, David Y. Munzenrider, John E. Grabowski, Eric Rodriguez-Galindo, Carlos Yock, Torunn I. Tarbell, Nancy J. Marcus, Karen J. Mukai, Shizuo MacDonald, Shannon M. TI Second Nonocular Tumors Among Survivors of Retinoblastoma Treated With Contemporary Photon and Proton Radiotherapy SO CANCER LA English DT Article DE proton; retinoblastoma; second malignancy; second cancer ID LONG-TERM SURVIVORS; EXTERNAL-BEAM RADIOTHERAPY; RADIATION-THERAPY; HEREDITARY RETINOBLASTOMA; FOLLOW-UP; RISK; CANCER; MORTALITY; CHILDREN; SARCOMA AB BACKGROUNDThe leading cause of death among patients with hereditary retinoblastoma is second malignancy. Despite its high rate of efficacy, radiotherapy (RT) is often avoided due to fear of inducing a secondary tumor. Proton RT allows for significant sparing of nontarget tissue. The current study compared the risk of second malignancy in patients with retinoblastoma who were treated with photon and proton RT. METHODSA retrospective review was performed of patients with retinoblastoma who were treated with proton RT at the Massachusetts General Hospital or photon RT at Boston Children's Hospital between 1986 and 2011. RESULTSA total of 86 patients were identified, 55 of whom received proton RT and 31 of whom received photon RT. Patients were followed for a median of 6.9 years (range, 1.0 years-24.4 years) in the proton cohort and 13.1 years (range, 1.4 years-23.9 years) in the photon cohort. The 10-year cumulative incidence of RT-induced or in-field second malignancies was significantly different between radiation modalities (proton vs photon: 0% vs 14%; P=.015). The 10-year cumulative incidence of all second malignancies was also different, although with borderline significance (5% vs 14%; P=.120). CONCLUSIONSRetinoblastoma is highly responsive to radiation. The central objection to the use of RT, the risk of second malignancy, is based on studies of patients treated with antiquated, relatively nonconformal techniques. The current study is, to the authors' knowledge, the first to present a series of patients treated with the most conformal of the currently available external-beam RT modalities. Although longer follow-up is necessary, the preliminary data from the current study suggest that proton RT significantly lowers the risk of RT-induced malignancy. Cancer 2014;120:126-133. (c) 2013 American Cancer Society. The leading cause of death among patients with hereditary retinoblastoma is second malignancy. Compared with conventional photon techniques, proton radiotherapy appears to significantly reduce the rate of radiation-induced second malignancy in patients treated for retinoblastoma. C1 [Sethi, Roshan V.] Harvard Univ, Sch Med, Boston, MA USA. [Shih, Helen A.; Mouw, Kent W.; Munzenrider, John E.; Yock, Torunn I.; Tarbell, Nancy J.; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Petersen, Robert] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA USA. [Kim, David Y.; Mukai, Shizuo] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Grabowski, Eric] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Dept Pediat Oncol, Boston, MA USA. [Marcus, Karen J.] Boston Childrens Hosp, Dept Radiat Oncol, Boston, MA USA. RP MacDonald, SM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Yawkey 112, Boston, MA 02114 USA. EM smacdonald@partners.org FU Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX This research was supported by the Federal Share of program income earned by Massachusetts General Hospital on grant C06 CA059267, Proton Therapy Research and Treatment Center. NR 29 TC 30 Z9 31 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2014 VL 120 IS 1 BP 126 EP 133 DI 10.1002/cncr.28387 PG 8 WC Oncology SC Oncology GA 272EL UT WOS:000328443000019 PM 24122173 ER PT J AU Krishnan, MS Epstein-Peterson, Z Chen, YH Tseng, YD Wright, AA Temel, JS Catalano, P Balboni, TA AF Krishnan, Monica S. Epstein-Peterson, Zachary Chen, Yu-Hui Tseng, Yolanda D. Wright, Alexi A. Temel, Jennifer S. Catalano, Paul Balboni, Tracy A. TI Predicting Life Expectancy in Patients With Metastatic Cancer Receiving Palliative Radiotherapy: The TEACHH Model SO CANCER LA English DT Article DE life expectancy; metastatic; palliative; prediction; model ID SPINAL-CORD COMPRESSION; PROGNOSTIC-FACTORS; RADIATION-THERAPY; PROSPECTIVE COHORT; PERFORMANCE STATUS; BRAIN METASTASES; UNITED-STATES; SURVIVAL; VALIDATION; ONCOLOGY AB BACKGROUNDPredicting life expectancy (LE) in patients with metastatic cancer who are receiving palliative therapies is a difficult task. The purpose of the current study was to develop a LE prediction model among patients receiving palliative radiotherapy (RT) that identifies those patients with short (<3 months) and long (>1 year) LEs. METHODSThe records of 862 patients with metastatic cancer receiving palliative RT at the Dana-Farber/Brigham and Women's Cancer Center between June 2008 and July 2011 were retrospectively reviewed. Cox proportional hazards models were used to evaluate established and potential clinical predictors of LE to construct a model predicting LE of <3 months and >1 year. RESULTSThe median survival was 5.6 months. On multivariate analysis, factors found to be significantly associated with a shorter LE were cancer type (lung and other vs breast and prostate), older age (>60 years vs 60 years), liver metastases, Eastern Cooperative Oncology Group performance status (2-4 vs 0-1), hospitalizations within 3 months before palliative RT (0 vs 1), and prior palliative chemotherapy courses (2 vs 0-1). Patients were divided into 3 groups with distinct median survivals: group A (those with 0-1 risk factors), 19.9 months (95% confidence interval [95% CI, 13.9 months-31.1months]); group B (those with 2-4 risk factors), 5.0 months (95% CI, 4.3 months -5.6 months); and group C (those with 5-6 risk factors), 1.7 months (95% CI, 1.2 months-2.1 months). CONCLUSIONSThe TEACHH model (type of cancer, Eastern Cooperative Oncology Group performance status, age, prior palliative chemotherapy, prior hospitalizations, and hepatic metastases) divides patients receiving palliative RT into 3 distinct LE groups at clinically informative extremes of the LE spectrum. It holds promise to assist radiation oncologists in tailoring palliative therapies to a patient's LE. Cancer 2014;120:134-141. (c) 2013 American Cancer Society. Predicting prognosis in patients receiving radiotherapy is a difficult task, but is particularly important for those patients at the extremes of the prognostic spectrum. The TEACHH model (type of cancer, Eastern Cooperative Oncology Group performance status, age, prior palliative chemotherapy, prior hospitalizations, and hepatic metastases), developed in the current study, is a prognostic tool that can aid physicians in identifying these patients. C1 [Krishnan, Monica S.; Tseng, Yolanda D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Epstein-Peterson, Zachary; Wright, Alexi A.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yu-Hui; Catalano, Paul; Balboni, Tracy A.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02155 USA. [Wright, Alexi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02155 USA. [Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Catalano, Paul] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Krishnan, MS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02155 USA. EM mkrishnan@lroc.harvard.edu FU American Society of Clinical Oncology Conquer Cancer Foundation FX This research was supported by an American Society of Clinical Oncology Conquer Cancer Foundation Career Development Award to Tracy A. Balboni MD, MPH. NR 38 TC 14 Z9 14 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2014 VL 120 IS 1 BP 134 EP 141 DI 10.1002/cncr.28408 PG 8 WC Oncology SC Oncology GA 272EL UT WOS:000328443000020 PM 24122413 ER PT J AU Jia, B Choy, E Cote, G Harmon, D Ye, SN Kan, QC Mankin, H Hornicek, F Duan, ZF AF Jia, Bin Choy, Edwin Cote, Gregory Harmon, David Ye, Shunan Kan, Quancheng Mankin, Henry Hornicek, Francis Duan, Zhenfeng TI Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells SO CANCER LETTERS LA English DT Article DE Kinase; Liposarcoma; CDK11; Tissue microarray; Immunohistochemistry ID ADVANCED SOLID TUMORS; SOFT-TISSUE SARCOMA; I CLINICAL-TRIAL; PHASE-I; DEDIFFERENTIATED LIPOSARCOMA; INHIBITOR FLAVOPIRIDOL; C-JUN; OSTEOSARCOMA; EXPRESSION; COMPLEXES AB Liposarcoma is the second most common soft tissue sarcoma in adults, but treatment options have been quite limited thus far. In this study, we investigated the functional and therapeutic relevance of cyclin-dependent kinase 11 (CDK11) as a putative target in liposarcoma. CDK11 knockdown by synthetic siRNA or lentiviral shRNA decreased cell proliferation, and induced apoptosis in liposarcoma cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of doxorubicin to inhibit cell growth in liposarcoma cells. These findings suggest that CDK11 is critical for the growth and proliferation of liposarcoma cells. CDK11 may be a promising therapeutic target for the treatment of liposarcoma patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Jia, Bin; Choy, Edwin; Cote, Gregory; Harmon, David; Ye, Shunan; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Jia, Bin; Choy, Edwin; Cote, Gregory; Harmon, David; Ye, Shunan; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA USA. [Jia, Bin; Kan, Quancheng] Zhengzhou Univ, Affiliated Hosp 1, Dept Pharmacol, Zhengzhou 450052, Henan, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, 100 Blossom St Jackson 1115, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084; Cote, Gregory/0000-0003-0181-886X FU Jeff Guyer Fund; Gattegno and Wechsler funds, the Kenneth Stanton Fund; Sarcoma Foundation of America (SFA); Chordoma Foundation; National Cancer Institute (NCI)/National Institutes of Health (NIH) [CA 151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopaedics; China Scholarship Council FX This work was supported, in part, by a grant from the Jeff Guyer Fund. Support has also been provided by the Gattegno and Wechsler funds, the Kenneth Stanton Fund. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA), a grant from Chordoma Foundation, a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452-01, a pilot grant from Sarcoma SPORE/NIH, and a grant from an Academic Enrichment Fund of MGH Orthopaedics. Dr. Jia is supported by Scholarship from China Scholarship Council. NR 43 TC 12 Z9 14 U1 0 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD JAN 1 PY 2014 VL 342 IS 1 BP 104 EP 112 DI 10.1016/j.canlet.2013.08.040 PG 9 WC Oncology SC Oncology GA 274FB UT WOS:000328591100012 PM 24007862 ER PT J AU Kim, KY Hwang, YJ Jung, MK Choe, J Kim, Y Kim, S Lee, CJ Ahn, H Lee, J Kowall, NW Kim, YK Kim, JI Lee, SB Ryu, H AF Kim, K. Y. Hwang, Y. J. Jung, M-K Choe, J. Kim, Y. Kim, S. Lee, C-J Ahn, H. Lee, J. Kowall, N. W. Kim, Y. K. Kim, J-I Lee, S. B. Ryu, H. TI A multifunctional protein EWS regulates the expression of Drosha and microRNAs SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE EWS; Drosha; microRNA; CTGF; dermal development ID TISSUE GROWTH-FACTOR; SARCOMA GENE EWS; EWINGS-SARCOMA; COMPLEX; INTEGRATION; COLLAGENS; IV AB EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (CoI4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of CoI4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of CoI4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of CoI4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis. C1 [Kim, K. Y.; Hwang, Y. J.; Jung, M-K; Kim, Y.] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea. [Choe, J.; Kim, Y. K.] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Kim, S.; Lee, C-J] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea. [Kim, S.; Ahn, H.] Seoul Natl Univ, Dept Comp Sci & Engn, Seoul, South Korea. [Kim, S.; Ahn, H.] Seoul Natl Univ, Bioinformat Inst, Seoul, South Korea. [Lee, J.; Kowall, N. W.; Ryu, H.] Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA. [Lee, J.; Kowall, N. W.; Ryu, H.] Boston Univ, Sch Med, Boston Univ Alzheimers Dis Ctr, Boston, MA 02118 USA. [Lee, J.; Kowall, N. W.; Ryu, H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kim, J-I] Seoul Natl Univ, Coll Med, Genome Med Inst, Seoul, South Korea. [Kim, J-I] Seoul Natl Univ, Coll Med, Dept Biochem, Seoul, South Korea. [Lee, S. B.] Tulane Univ, Sch Med, Dept Pathol & Lab Med, New Orleans, LA 70112 USA. [Ryu, H.] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul, South Korea. RP Ryu, H (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol, Bldg 1A,Rm109,150 South Huntington Ave, Boston, MA 02130 USA. EM hoonryu@bu.edu RI KIM, JONG-IL/D-1019-2011; Kowall, Neil/G-6364-2012 OI KIM, JONG-IL/0000-0002-7240-3744; Kowall, Neil/0000-0002-6624-0213 FU Korea Institute of Science and Technology [2E24320]; NIH [NS 067283-01A1] FX We thank Dr. V Narry Kim for providing Drosha, DGCR8, and Dicer plasmids and Dr. Fukamizu for providing EWS plasmid. We also thank Elizabeth (Eun Kyung) Park (Boston University School of Medicine) for the preparation of manuscript. This study was supported by Brain Science Flagship Grant (2E24320) (HR) from Korea Institute of Science and Technology and NIH Grant (NS 067283-01A1) (HR). NR 29 TC 9 Z9 9 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2014 VL 21 IS 1 SI SI BP 136 EP 145 DI 10.1038/cdd.2013.144 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 274QV UT WOS:000328622100015 PM 24185621 ER PT J AU El-Serag, HB Xu, F Biyani, P Cooper, GS AF El-Serag, Hashem B. Xu, Fang Biyani, Prachi Cooper, Gregory S. TI Bundling in Medicare Patients Undergoing Bidirectional Endoscopy: How Often Does It Happen? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Medicare; Insurance; Colonoscopy; Health Services Research. ID UPPER GASTROINTESTINAL ENDOSCOPY; OCCULT BLOOD-TEST; NEGATIVE COLONOSCOPY; ASYMPTOMATIC PATIENTS; POSITIVE STOOL; CLAIMS; YIELD AB BACKGROUND & AIMS: In patients with appropriate indications, performance of both colonoscopy and esophagogastroduodenoscopy (EGD) at the same time (bundling) is convenient for patients, efficient for providers, and cost saving for the health care system. However, Medicare reimbursement for bundled procedures is at a rate that is less than the sum of the 2 procedures when charged separately, and this may create a disincentive to bundle. The practice patterns of bundling are unknown at a US population-based level. METHODS: We examined Medicare claims from 2007 to 2009 from the Carrier file in a national, random sample of fee-for-service beneficiaries aged 66 and older. We identified patients who had both a colonoscopy and EGD performed within 180 days of each other and calculated the proportions of patients with both procedures bundled on the same date, within 1 to 30 days, and within 31 to 180 days of each other. We compared patients in these 3 groups for demographics and clinical indications for the procedures (bleeding, lower or upper gastrointestinal symptoms, surveillance, and screening). RESULTS: We identified 12,982 Medicare-enrolled individuals who had a colonoscopy and an EGD performed within 180 days of each other. Approximately 35% of procedures were not bundled on the same day, and, of these, 2359 (18%) were performed within 30 days of each other, and 2219 (17%) were performed within 31 to 180 days of each other. There were marked geographic differences in the percentage of bundling, with the lowest occurrence in the Northeast and the highest in the West. Patients with bundled procedures were more likely to have gastrointestinal bleeding and less likely to have screening or surveillance indications. CONCLUSIONS: Although same-day bundling of endoscopic procedures offers a number of advantages, it is not practiced in more than one-third of cases in a national sample of Medicare beneficiaries. C1 [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Xu, Fang; Biyani, Prachi; Cooper, Gregory S.] Case Western Reserve Univ, Div Gastroenterol, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Xu, Fang; Biyani, Prachi; Cooper, Gregory S.] Case Western Reserve Univ, Ctr Comprehens Canc, Cleveland, OH 44106 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K24-04-107]; National Institutes of Health/National Cancer Institute [R01 116845]; Houston VA Health Services Research & Development Center of Excellence [HFP90-020]; Texas Digestive Disease Center National Institutes of Health [DK58338]; NCI [R01 132862]; National Center for Advancing Translational Sciences [UL1TR000439] FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant K24-04-107 (H.E.-S.). This work was funded in part by a grant from the National Institutes of Health/National Cancer Institute (R01 116845), the Houston VA Health Services Research & Development Center of Excellence (HFP90-020), and the Texas Digestive Disease Center National Institutes of Health (DK58338). Also supported by grant NCI R01 132862 and by the National Center for Advancing Translational Sciences (UL1TR000439) (G.C.). NR 11 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2014 VL 12 IS 1 BP 58 EP 63 DI 10.1016/j.cgh.2013.07.021 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 276FQ UT WOS:000328734300012 PM 23911874 ER PT J AU Bielawska, B Day, AG Lieberman, DA Hookey, LC AF Bielawska, Barbara Day, Andrew G. Lieberman, David A. Hookey, Lawrence C. TI Risk Factors for Early Colonoscopic Perforation Include Non-Gastroenterologist Endoscopists: A Multivariable Analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE ASA Classification; GI; Intestine; Quality Control; Endoscopy Training ID NURSE-ADMINISTERED PROPOFOL; GENERAL-SURGERY RESIDENTS; POPULATION-BASED-ANALYSIS; SURGICAL-MANAGEMENT; COLORECTAL CANCERS; ANESTHESIA; SEDATION; OUTCOMES; COMPLICATIONS; PERFORMANCE AB BACKGROUND & AIMS: Bowel perforation is a rare but serious complication of colonoscopy. Its prevalence is increasing with the rapidly growing volume of procedures performed. Although colonoscopies have been performed for decades, the risk factors for perforation are not completely understood. We investigated risk factors for perforation during colonoscopy by assessing variables that included sedation type and endoscopist specialty and level of training. METHODS: We performed a retrospective multivariate analysis of risk factors for early perforation (occurring at any point during the colonoscopy but recognized during or immediately after the procedure) in adult patients by using the Clinical Outcomes Research Initiative National Endoscopic Database. Risk factors were determined from published articles. Additional variables assessed included endoscopist specialty and years of experience, trainee involvement, and sedation with propofol. RESULTS: We identified 192 perforation events during 1,144,900 colonoscopies from 85 centers entered into the database from January 2000-March 2011. On multivariate analysis, increasing age, American Society of Anesthesia class, female sex, hospital setting, any therapy, and polyps >10 mm were significantly associated with increased risk of early perforation. Colonoscopies performed by surgeons and endoscopists of unknown specialty had higher rates of perforation than those performed by gastroenterologists (odds ratio, 2.00; 95% confidence interval, 1.30-3.08). Propofol sedation did not significantly affect risk for perforation. CONCLUSIONS: In addition to previously established risk factors, non-gastroenterologist specialty was found to affect risk for perforations detected during or immediately after colonoscopy. This finding could result from differences in volume and style of endoscopy training. Further investigation into these observed associations is warranted. C1 [Bielawska, Barbara; Hookey, Lawrence C.] Queens Univ, Gastrointestinal Dis Res Unit, Kingston, ON K7L 5G2, Canada. [Day, Andrew G.] Kingston Gen Hosp, Clin Res Ctr, Kingston, ON K7L 2V7, Canada. [Lieberman, David A.] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland Vet Affairs Med Ctr, Portland, OR USA. RP Hookey, LC (reprint author), Queens Univ, Div Gastroenterol, Dept Med, Hotel Dieu Hosp, Kingston, ON K7L 5G2, Canada. EM hookeyl@hdh.kari.net FU NIDDK [U01DK57132, R33-DK61778-01, R21-CA131626] FX This project was supported with funding from NIDDK U01DK57132, R33-DK61778-01, and R21-CA131626. In addition, the practice network (Clinical Outcomes Research Initiative) has received support from the following entities to support the infrastructure of the practice-based network: AstraZeneca, Novartis, Bard International, Pentax USA, ProVation, Endosoft, GIVEN Imaging, and Ethicon. The commercial entities had no involvement in this research. NR 32 TC 23 Z9 24 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2014 VL 12 IS 1 BP 85 EP 92 DI 10.1016/j.cgh.2013.06.030 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 276FQ UT WOS:000328734300016 PM 23891916 ER PT J AU Gu, X Hou, JB Yang, S Yu, H Tian, JW Liu, F Li, N Yu, B Jang, IK AF Gu, Xia Hou, Jingbo Yang, Shuang Yu, Huai Tian, Jinwei Liu, Fang Li, Ning Yu, Bo Jang, Ik-Kyung TI Is lipoprotein-associated phospholipase A2 activity correlated with fibrous-cap thickness and plaque volume in patients with acute coronary syndrome? SO CORONARY ARTERY DISEASE LA English DT Article DE fibrous-cap thickness; inflammation; lipoprotein-associated phospholipase A(2); optical coherence tomography ID OPTICAL COHERENCE TOMOGRAPHY; ACETYLHYDROLASE ACTIVITY; ATHEROSCLEROTIC PLAQUE; CLINICAL-APPLICATION; ARTERY-DISEASE; A(2) ACTIVITY; RISK; DARAPLADIB AB BackgroundLipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a specific biomarker specific for vascular inflammation. Inflammation has a significant association with plaque progression. The fibrous-cap thickness (FCT) is one of the major determinants of plaque vulnerability in atherosclerotic plaques. However, data on the relationship between Lp-PLA(2) activity and FCT in lipid plaque are limited. This study aimed to evaluate the in-vivo association between changes in Lp-PLA(2) activity and FCT and plaque volume in patients with acute coronary syndrome (ACS).Patients and methodsTwenty-four consecutive patients with ACS were enrolled between May 2010 and May 2012. The plaque volume and FCT of nonculprit lipid-rich plaques were assessed by intravascular ultrasound and optical coherence tomography, respectively, at baseline and after 12 months. Lp-PLA(2) activity was determined using the colorimetric assay kit.ResultsDuring the 12 months of observation, FCT increased significantly from baseline to follow-up, with a mean percent change of 74.446.8%. A significant correlation was observed between changes in Lp-PLA(2) activity and changes in FCT (r=-0.56, P=0.006). Changes in plaque volume were also correlated significantly with changes in Lp-PLA(2) activity during the study period (r=0.52, P=0.01).ConclusionSignificant associations between serial changes in Lp-PLA(2) activity and changes in FCT and plaque volume were observed in patients with ACS. C1 [Gu, Xia; Hou, Jingbo; Yang, Shuang; Yu, Huai; Tian, Jinwei; Liu, Fang; Li, Ning; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Peoples R China. [Gu, Xia; Hou, Jingbo; Yang, Shuang; Tian, Jinwei; Liu, Fang; Li, Ning; Yu, Bo] Chinese Minist Educ, Key Labs Myocardial Ischemia, Harbin, Peoples R China. [Tian, Jinwei; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Peoples R China. EM yubodr2009@163.com FU National Natural Science Foundation of China [81171430/H1816, 81300201]; China Postdoctoral Science Foundation [2013M531074] FX B.Y. was supported by Grant number 81171430/H1816 from the National Natural Science Foundation of China. J.T. has received a grant from the National Natural Science Foundation of China (81300201) and a grant from China Postdoctoral Science Foundation (2013M531074). NR 24 TC 2 Z9 2 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD JAN PY 2014 VL 25 IS 1 BP 10 EP 15 DI 10.1097/MCA.0000000000000041 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 274TW UT WOS:000328630100003 PM 24089018 ER PT J AU Moromizato, T Litonjua, AA Braun, AB Gibbons, FK Giovannucci, E Christopher, KB AF Moromizato, Takuhiro Litonjua, Augusto A. Braun, Andrea B. Gibbons, Fiona K. Giovannucci, Edward Christopher, Kenneth B. TI Association of Low Serum 25-Hydroxyvitamin D Levels and Sepsis in the Critically III SO CRITICAL CARE MEDICINE LA English DT Article DE intensive care; mortality; vitamin D ID VITAMIN-D DEFICIENCY; REGULATORY T-CELLS; INTENSIVE-CARE-UNIT; ACUTE KIDNEY INJURY; 1,25-DIHYDROXYVITAMIN D-3; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; CYTOKINE PRODUCTION; ILL PATIENTS; INCREASED MORTALITY; MEDICAL INPATIENTS AB Objective: We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with sepsis in the critically ill. Design: Two-center observational study of patients treated in medical and surgical ICUs. Setting: Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, MA. Patients: Three thousand three hundred eighty-six patients, 18 years old or older, in whom 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2011. Interventions: None Measurements and Main Results: Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D ( 15 ng/mL), insufficiency (15-30 ng/mL), and sufficiency ( 30 ng/mL). The primary outcome was sepsis as defined by International Classification of Diseases, 9th Edition, Clinical Modification and validated by the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society, and Surgical Infection Society international sepsis definitions conference guidelines. Logistic regression examined the presence of sepsis 3 days prior to critical care initiation to 7 days after critical care initiation. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for the risk of sepsis. In the full cohort, 25-hydroxyvitamin D deficiency is a significant predictor for the risk of International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Deyo-Charlson index (adjusted odds ratio, 1.51 [95% CI, 1.17-1.94]; p = 0.001) relative to patients with 25-hydroxyvitamin D sufficiency. In a subset of cohort patients enriched for those with International Classification of Diseases, 9th Edition, Clinical Modification-diagnosed sepsis (n = 444), preadmission 25-hydroxyvitamin D deficiency is a significant predictor for the risk of conference guideline-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Acute Physiology and Chronic Health Evaluation II (adjusted odds ratio, 2.05 [95% CI, 1.19-3.52]; p = 0.009) relative to patients with 25-hydroxyvitamin D sufficiency. Furthermore, in cohort patients with International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis (n = 568), the multivariable adjusted risk of 90-day mortality was 1.6-fold higher in those with preadmission 25-hydroxyvitamin D values in the insufficient and deficient range, compared with those with preadmission vitamin D sufficiency (adjusted odds ratio, 1.63 [95% CI, 1.11-2.39]; p = 0.01). Conclusion: 25-hydroxyvitamin D deficiency prior to hospital admission is a significant predictor of sepsis in the critically ill. Additionally, patients with sepsis who are not vitamin D sufficient have an increased risk of mortality following critical care initiation. C1 [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Braun, Andrea B.; Gibbons, Fiona K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. EM kchristopher@partners.org FU National Institutes of Health (NIH); NIH; Brigham Renal Review Course and Harvard CME FX Dr. Litonjua has received grant support from National Institutes of Health (NIH), receives royalties from UpToDate, and receives discount of books (editor royalties) from Springer-Humana Press. Dr. Giovannucci is the editor-in chief of Cancer Causes and Control. Dr. Christopher has received grant support for the NIH and has received payment for lectures from Brigham Renal Review Course and Harvard CME. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 97 TC 53 Z9 61 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2014 VL 42 IS 1 BP 97 EP 107 DI 10.1097/CCM.0b013e31829eb7af PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 274OK UT WOS:000328615600032 PM 23982028 ER PT J AU Pendergraft, WF Niles, JL AF Pendergraft, William F., III Niles, John L. TI Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE antineutrophil cytoplasmic autoantibody; cocaine; hydralazine; minocycline; propylthiouracil ID ANTIBODY-ASSOCIATED VASCULITIS; INDUCED AUTOIMMUNE-DISEASE; SMALL-VESSEL VASCULITIS; WEGENERS-GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; POSITIVE VASCULITIS; CRESCENTIC GLOMERULONEPHRITIS; EPIGENETIC THERAPY; COCAINE ADULTERANT; RENAL VASCULITIS AB Purpose of reviewAntineutrophil cytoplasmic autoantibody (ANCA) vasculitis is a systemic autoimmune disease resulting in small-vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 or myeloperoxidase. Legal drug culprits have been implicated as causative agents in secondary forms of disease, and a recent burst of reports also implicate levamisole-adulterated cocaine as a culprit.Recent findingsHere, we briefly discuss all drug culprits associated with ANCA vasculitis and then focus on clinical, serologic, therapeutic and mechanistic aspects of four main drug culprits receiving attention of late, namely hydralazine, minocycline, propylthiouracil (PTU) and levamisole-adulterated cocaine.SummaryHydralazine, minocycline, propylthiouracil and levamisole-adulterated cocaine use should be closely considered in any patient where ANCA vasculitis is entertained given the wide use of these drugs in the community. Furthermore, medical practitioners should test urine for the presence of cocaine in any patient with presumed ANCA vasculitis, and if positive, then urine should also be tested for levamisole. Clinical features can be severe requiring not only drug cessation and supportive care, but also immunosuppression, plasma exchange in severe cases and dialysis as needed. Clinical trial investigators should strongly consider excluding patients with drug-induced forms of disease and mechanistic inroads are greatly needed in these secondary forms of disease to help elucidate the underlying cause and pathogenesis of ANCA vasculitis. C1 [Pendergraft, William F., III] Brigham & Womens Hosp, Joint Nephrol Fellowship Program, Boston, MA 02115 USA. [Pendergraft, William F., III] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pendergraft, William F., III; Niles, John L.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Pendergraft, William F., III; Niles, John L.] Massachusetts Gen Hosp, Vasculitis & Glomerulonephritis Clin, Div Nephrol, Boston, MA 02114 USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 151 Merrimac St,Floor 3, Boston, MA 02114 USA. EM jlniles@partners.org FU Genentech; NIDDK [1 F32 DK097891-01]; Alexion Pharmaceuticals FX W.F.P. has no conflicts of interest. J.L.N. has served as a rituximab-specific advisory board member for Genentech and is currently participating in the Genentech-sponsored RAVER study and receiving clinical research funding from Alexion Pharmaceuticals.; W.F.P. is supported by NIDDK 1 F32 DK097891-01. NR 67 TC 25 Z9 26 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2014 VL 26 IS 1 BP 42 EP 49 DI 10.1097/BOR.0000000000000014 PG 8 WC Rheumatology SC Rheumatology GA 277KR UT WOS:000328818500007 PM 24276086 ER PT J AU He, KH Juhl, K Karadimos, M El Khattabi, I Fitzpatrick, C Bonner-Weir, S Sharma, A AF He, KaiHui Hu Juhl, Kirstine Karadimos, Michael El Khattabi, Ilham Fitzpatrick, Connor Bonner-Weir, Susan Sharma, Arun TI Differentiation of pancreatic endocrine progenitors reversibly blocked by premature induction of MafA SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Differentiation of endocrine progenitors; Transcription factor MafA; beta-Cell maturation ID EMBRYONIC STEM-CELLS; BETA-CELLS; IN-VIVO; EXPRESSION; MICE; COMPETENCE; MATURATION; GENERATION; REGULATOR; ISLETS AB Specification and maturation of insulin(+) cells accompanies a transition in expression of Maf family of transcription factors. In development, MafA is expressed after specification of insulin(+) cells that are expressing another Maf factor, MafB; after birth, these insulin(+) MafA(+) cells stop MafB expression and gain glucose responsiveness. Current differentiation protocols for deriving insulin-producing beta-cells from stem cells result in beta-cells lacking both MafA expression and glucose-stimulated insulin secretion. So driving expression of MafA, a beta-cell maturation factor in endocrine precursors could potentially generate glucose-responsive MafA(+) beta cells. Using inducible transgenic mice, we characterized the final stages of beta-cell differentiation and maturation with MafA pause/release experiments. We found that forcing MafA transgene expression, out of its normal developmental context, in Ngn3(+) endocrine progenitors blocked endocrine differentiation and prevented the formation of hormone(+) cells. However, this arrest was reversible such that with stopping the transgene expression, the cells resumed their differentiation to hormone(+) cells, including alpha-cells, indicating that the block likely occurred after progenitors had committed to a specific hormonal fate. Interestingly, this delayed resumption of endocrine differentiation resulted in a greater proportion of immature insulin(+)MafB(+) cells at P5, demonstrating that during maturation the inhibition of MafB in beta-cell transitioning from insulin(+)MafB(+) to insulin(+)Mafb(-) stage is regulated by cell-autonomous mechanisms. These results demonstrate the importance of proper context of initiating MafA expression on the endocrine differentiation and suggest that generating mature Insulin(+)MafA(+) beta-cells will require the induction of MafA in a narrow temporal window to achieve normal endocrine differentiation. (C) 2013 Elsevier Inc. All rights reserved. C1 [He, KaiHui Hu; Juhl, Kirstine; Karadimos, Michael; El Khattabi, Ilham; Fitzpatrick, Connor; Bonner-Weir, Susan; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. RP Sharma, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02115 USA. EM arun.sharma@joslin.harvard.edu FU NIH [RO1 DK060127]; Juvenile Diabetes Research Foundation; American Diabetes Association [1-12-BS-187]; Herbert Graetz Fund; Shirley and William Fleisher Family Foundation; Alexander and Margaret Stewart Trust; Swiss National Foundation [PBGEP3-121298]; Lundbeckfonden [R7-A714-B576]; Media, Advanced Microscopy, Advanced Genomics/Genetics, and Bioinformatics Cores of Joslin Diabetes Endocrinology Research Center [NIH DK-36836]; [NIH-P30-HD-18655] FX We thank Drs. Chris Wright and Roland Stein (Vanderbilt University) for their constructive criticisms of the manuscript. We thank Taliesin Lenhart (Harvard Stem Cell Institute, Summer Internship program) for assistance with immunostaining and quantification of images; Dr. Anthony Hill, IDDRC Imaging Core Children's Hospital Boston and grant NIH-P30-HD-18655, for assistance with Volocity software.; This study was supported by research grants from NIH (RO1 DK060127), Juvenile Diabetes Research Foundation, American Diabetes Association grant 1-12-BS-187, the Herbert Graetz Fund, Shirley and William Fleisher Family Foundation, and the Alexander and Margaret Stewart Trust to AS; post-doctoral fellowships from Swiss National Foundation (PBGEP3-121298) to KH HH and from Lundbeckfonden (#R7-A714-B576) to KJ; and the Media, Advanced Microscopy, Advanced Genomics/Genetics, and Bioinformatics Cores of Joslin Diabetes Endocrinology Research Center (NIH DK-36836). NR 30 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2014 VL 385 IS 1 BP 2 EP 12 DI 10.1016/j.ydbio.2013.10.024 PG 11 WC Developmental Biology SC Developmental Biology GA 277CN UT WOS:000328796100002 ER PT J AU Biessels, GJ Reijmer, YD AF Biessels, Geert Jan Reijmer, Yael D. TI Brain MRI in Children With Type 1 Diabetes: Snapshot or Road Map of Developmental Changes? SO DIABETES LA English DT Editorial Material ID HYPERGLYCEMIA; CHILDHOOD; ONSET; YOUTH; LIFE C1 [Biessels, Geert Jan; Reijmer, Yael D.] Univ Med Ctr, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Reijmer, Yael D.] Massachusetts Gen Hosp, Harvard Med Sch, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. RP Biessels, GJ (reprint author), Univ Med Ctr, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. EM g.j.biessels@umcutrecht.nl NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JAN PY 2014 VL 63 IS 1 BP 62 EP 64 DI 10.2337/db13-1466 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275MF UT WOS:000328680400013 PM 24357700 ER PT J AU Dirice, E Kahraman, S Jiang, WY El Ouaamari, A De Jesus, DF Teo, AKK Hu, J Kawamori, D Gaglia, JL Mathis, D Kulkarni, RN AF Dirice, Ercument Kahraman, Sevim Jiang, Wenyu El Ouaamari, Abdelfattah De Jesus, Dario F. Teo, Adrian K. K. Hu, Jiang Kawamori, Dan Gaglia, Jason L. Mathis, Diane Kulkarni, Rohit N. TI Soluble Factors Secreted by T Cells Promote beta-Cell Proliferation SO DIABETES LA English DT Article ID NONOBESE DIABETIC MOUSE; HUMAN PANCREATIC-ISLETS; DENDRITIC CELLS; MICE; PREVENTS; MASS; REGENERATION; LYMPHOCYTES; MODEL; ONSET AB Type 1 diabetes is characterized by infiltration of pancreatic islets with immune cells, leading to insulin deficiency. Although infiltrating immune cells are traditionally considered to negatively impact -cells by promoting their death, their contribution to proliferation is not fully understood. Here we report that islets exhibiting insulitis also manifested proliferation of -cells that positively correlated with the extent of lymphocyte infiltration. Adoptive transfer of diabetogenic CD4(+) and CD8(+) T cells, but not B cells, selectively promoted -cell proliferation in vivo independent from the effects of blood glucose or circulating insulin or by modulating apoptosis. Complementary to our in vivo approach, coculture of diabetogenic CD4(+) and CD8(+) T cells with NOD.RAG1(-/-) islets in an in vitro transwell system led to a dose-dependent secretion of candidate cytokines/chemokines (interleukin-2 [IL-2], IL-6, IL-10, MIP-1, and RANTES) that together enhanced -cell proliferation. These data suggest that soluble factors secreted from T cells are potential therapeutic candidates to enhance -cell proliferation in efforts to prevent and/or delay the onset of type 1 diabetes. C1 [Dirice, Ercument; Kahraman, Sevim; El Ouaamari, Abdelfattah; De Jesus, Dario F.; Teo, Adrian K. K.; Hu, Jiang; Kawamori, Dan; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. [Dirice, Ercument; Kahraman, Sevim; El Ouaamari, Abdelfattah; De Jesus, Dario F.; Teo, Adrian K. K.; Hu, Jiang; Kawamori, Dan; Gaglia, Jason L.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA USA. [Jiang, Wenyu] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gaglia, Jason L.] Joslin Diabet Ctr, Sect Immunobiol, Boston, MA 02215 USA. [Mathis, Diane] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Teo, Adrian/A-4009-2013; Dirice, Ercument/B-2825-2017; OI Teo, Adrian/0000-0001-5901-7075; Gaglia, Jason/0000-0003-2904-312X; Kahraman, Sevim/0000-0002-2880-6589 FU Juvenile Diabetes Research Foundation [3-2010-474]; Turkish Diabetes, Obesity and Nutrition Association; NIH [RO1-DK-67536]; Diabetes Research Center [NIH P30-DK-036836, NIH PO1-AI-054904] FX This work was supported by a Juvenile Diabetes Research Foundation Fellowship (3-2010-474) and Turkish Diabetes, Obesity and Nutrition Association Novartis Science Award to E. D. Some of the reagents were supported by NIH Grant RO1-DK-67536 to R.N.K., and the Joslin Diabetes Center Flow Cytometry Cores were supported by Diabetes Research Center Grant NIH P30-DK-036836 and NIH PO1-AI-054904 to D. M. NR 50 TC 25 Z9 25 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JAN PY 2014 VL 63 IS 1 BP 188 EP 202 DI 10.2337/db13-0204 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275MF UT WOS:000328680400026 PM 24089508 ER PT J AU Raeder, H McAllister, FE Tjora, E Bhatt, S Haldorsen, I Hu, J Willems, SM Vesterhus, M El Ouaamari, A Liu, M Raeder, MB Immervoll, H Hoem, D Dimcevski, G Njolstad, PR Molven, A Gygi, SP Kulkarni, RN AF Raeder, Helge McAllister, Fiona E. Tjora, Erling Bhatt, Shweta Haldorsen, Ingfrid Hu, Jiang Willems, Stefan M. Vesterhus, Mette El Ouaamari, Abdelfattah Liu, Manway Raeder, Maria B. Immervoll, Heike Hoem, Dag Dimcevski, Georg Njolstad, Pal R. Molven, Anders Gygi, Steven P. Kulkarni, Rohit N. TI Carboxyl-Ester Lipase Maturity-Onset Diabetes of the Young Is Associated With Development of Pancreatic Cysts and Upregulated MAPK Signaling in Secretin-Stimulated Duodenal Fluid SO DIABETES LA English DT Article ID EXOCRINE DYSFUNCTION; MUTATIONS; DISEASE; GENE; EXPRESSION; TANDEM; TARGET; CANCER; ASSAY; CELL AB Carboxyl-ester lipase (CEL) maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes and pancreatic exocrine dysfunction due to mutations in the CEL gene encoding CEL. The pathogenic mechanism for diabetes development is unknown. Since CEL is expressed mainly in pancreatic acinar cells, we asked whether we could find structural pancreatic changes in CEL-MODY subjects during the course of diabetes development. Furthermore, we hypothesized that the diseased pancreas releases proteins that are detectable in pancreatic fluid and potentially reflect activation or inactivation of disease-specific pathways. We therefore investigated nondiabetic and diabetic CEL-mutation carriers by pancreatic imaging studies and secretin-stimulated duodenal juice sampling. The secretin-stimulated duodenal juice was studied using cytokine assays, mass spectrometry (MS) proteomics, and multiplexed MS-based measurement of kinase activities. We identified multiple pancreatic cysts in all eight diabetic mutation carriers but not in any of the four nondiabetic mutation carriers or the six healthy controls. Furthermore, we identified upregulated mitogen-activated protein kinase (MAPK) target proteins and MAPK-driven cytokines and increased MAPK activity in the secretin-stimulated duodenal juice. These findings show that subjects with CEL-MODY develop multiple pancreatic cysts by the time they develop diabetes and that upregulated MAPK signaling in the pancreatic secretome may reflect the pathophysiological development of pancreatic cysts and diabetes. C1 [Raeder, Helge; Bhatt, Shweta; Hu, Jiang; El Ouaamari, Abdelfattah; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. [Raeder, Helge; Tjora, Erling; Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Raeder, Helge; Tjora, Erling; Raeder, Maria B.; Njolstad, Pal R.] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. [McAllister, Fiona E.; Willems, Stefan M.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Haldorsen, Ingfrid] Haukeland Hosp, Dept Radiol, N-5021 Bergen, Norway. [Haldorsen, Ingfrid] Univ Bergen, Dept Clin Med, Sect Radiol, Bergen, Norway. [Vesterhus, Mette; Dimcevski, Georg] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway. [Liu, Manway] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Immervoll, Heike; Molven, Anders] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway. [Immervoll, Heike; Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Immervoll, Heike] Alesund Hosp, Dept Pathol, Alesund, Norway. [Hoem, Dag] Haukeland Hosp, Dept Surg, N-5021 Bergen, Norway. RP Raeder, H (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. EM helge.rader@uib.no OI Haldorsen, Ingfrid S./0000-0001-9313-7564 FU Norwegian Research Council; Western Norway Regional Health Authority; Norwegian Endocrine Society; Fulbright Foundation; Innovest; University of Bergen; Norwegian Cancer Society; Joslin DRC Specialized Assay; Advanced Microscopy Cores [NIH P30 DK-36836]; National Institutes of Health [HG3456, RO1 DK-67536]; Graetz Bridge Funds FX This work was supported by the Norwegian Research Council (to H. R. and P.R.N.); the Western Norway Regional Health Authority (to H. R., H. I., and P.R.N.); the Norwegian Endocrine Society and the Fulbright Foundation (to H. R.); Innovest and the University of Bergen (to P.R.N.); the Norwegian Cancer Society (to A. M.); Joslin DRC Specialized Assay and Advanced Microscopy Cores (NIH P30 DK-36836), National Institutes of Health grant HG3456 (to S. P. G.), and National Institutes of Health grant RO1 DK-67536 and the Graetz Bridge Funds (to R.N.K.). NR 32 TC 10 Z9 12 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JAN PY 2014 VL 63 IS 1 BP 259 EP 269 DI 10.2337/db13-1012 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275MF UT WOS:000328680400032 PM 24062244 ER PT J AU Nathan, DM McGee, P Steffes, MW Lachin, JM AF Nathan, David M. McGee, Paula Steffes, Michael W. Lachin, John M. CA DCCT EDIC Res Grp TI Relationship of Glycated Albumin to Blood Glucose and HbA(1c) Values and to Retinopathy, Nephropathy, and Cardiovascular Outcomes in the DCCT/EDIC Study SO DIABETES LA English DT Article ID TYPE-1 DIABETES-MELLITUS; CASE-COHORT DESIGN; MICROVASCULAR COMPLICATIONS; INTENSIVE THERAPY; TRIAL; HEMOGLOBIN; RISK; INTERVENTIONS; EPIDEMIOLOGY; PROGRESSION AB The association of chronic glycemia, measured by HbA(1c), with long-term complications of type 1 diabetes has been well established in the Diabetes Control and Complications Trial (DCCT) and other studies. The role of intermediate-term and acute glycemia and of glucose variability on microvascular and cardiovascular disease (CVD) is less clear. In order to examine the interrelationships among long-term, intermediate-term, and acute measures of glucose and its daily variability, we compared HbA(1c), glycated albumin (GA), and seven-point glucose profile concentrations measured longitudinally in a case-cohort subpopulation of the DCCT. HbA(1c) and GA were closely correlated with each other and with the mean blood glucose (MBG) calculated from the seven-point profile. The associations of glucose variability and postprandial concentrations with HbA(1c) and GA were relatively weak and were further attenuated when MBG was included in multivariate models. In the case-cohort analyses, HbA(1c) and GA had similar associations with retinopathy and nephropathy, which were strengthened when both measures were considered together. Only HbA(1c) was significantly associated with CVD. The demonstrated interrelationships among different measures of glycemia will need to be considered in future analyses of their roles in the development of long-term complications of type 1 diabetes. C1 [Nathan, David M.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Nathan, David M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [McGee, Paula; Lachin, John M.] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP McGee, P (reprint author), George Washington Univ, Biostat Ctr, Rockville, MD USA. EM paulaf@bsc.gwu.edu FU DCCT/EDIC; Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute, the National Institute of Neurological Disorders and Stroke, the Genetic Clinical Research Centers Program; Clinical Translational Science Center Program, Bethesda, Maryland; Charlton Foundation for Innovative Diabetes Research; Asahi Kasei Pharma Corporation, Tokyo, Japan FX The DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1982-1993 and 2011-2016), contracts (1982-2011) with the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, and support from the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the Genetic Clinical Research Centers Program (1993-2007), and the Clinical Translational Science Center Program (2006-present), Bethesda, Maryland. D.M.N. was supported in part by the Charlton Foundation for Innovative Diabetes Research.; Industry contributors have provided free or discounted supplies or equipment to support participants' adherence to the study: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North America Headquarters, Tarrytown, NY), Becton Dickinson (Franklin Lakes, NJ), CanAm (Atlanta, GA), Eli Lilly (Indianapolis, IN), LifeScan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MI), Omron (Shelton, CT), OmniPod Insulin Management System (Bedford, MA), Roche Diabetes Care (Indianapolis, IN), and Sanofi (Bridgewater, NJ). The current ancillary project received support from Asahi Kasei Pharma Corporation, Tokyo, Japan, in the form of donated assay kits. NR 30 TC 38 Z9 41 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JAN PY 2014 VL 63 IS 1 BP 282 EP 290 DI 10.2337/db13-0782 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275MF UT WOS:000328680400034 PM 23990364 ER PT J AU Emhoff, IA Lee, GC Sylla, P AF Emhoff, Isha Ann Lee, Grace Clara Sylla, Patricia TI Transanal colorectal resection using natural orifice translumenal endoscopic surgery (NOTES) SO DIGESTIVE ENDOSCOPY LA English DT Review DE minimally invasive surgery; natural orifice translumenal endoscopic surgery (NOTES); rectal cancer; total mesorectal excision; transanal ID TOTAL MESORECTAL EXCISION; LOW ANTERIOR RESECTION; LOW RECTAL-CANCER; MINIMALLY INVASIVE SURGERY; AUTONOMIC NERVE PRESERVATION; RANDOMIZED CONTROLLED-TRIAL; SPECIMEN EXTRACTION; LOCAL EXCISION; LAPAROSCOPIC RESECTION; RISK-FACTORS AB The surgical management of rectal cancer has evolved over the past century, with total mesorectal excision (TME) emerging as standard of care. As a result of the morbidity associated with open TME, minimally invasive techniques have become popular. Natural orifice translumenal endoscopic surgery (NOTES) has been held as the next revolution in surgical techniques, offering the possibility of incisionless' TME. Early clinical series of transanal TME with laparoscopic assistance (n=72) are promising, with overall intraoperative and postoperative complication rates of 8.3% and 27.8%, respectively, similar to laparoscopic TME. The mesorectal specimen was intact in all patients, and 94.4% had negative margins. There was no oncological recurrence in average-risk patients at short-term follow up, and 2-year survivalrates in high-risk patients were comparable to that after laparoscopic TME. These preliminary studies demonstrate transanal NOTES TME with laparoscopic assistance to be clinically feasible and safe given careful patient selection, surgical expertise, and appropriate procedural training. We are hopeful that with optimization of transanal instruments and surgical techniques, pure transanal NOTES TME will become a viable alternative to open and laparoscopic TME in the future. C1 [Emhoff, Isha Ann; Lee, Grace Clara; Sylla, Patricia] Massachusetts Gen Hosp, Dept Surg, Div Gastrointestinal Surg, Boston, MA 02114 USA. RP Sylla, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Gastrointestinal Surg, 15 Parkman St,Wang 460, Boston, MA 02114 USA. EM psylla@partners.org NR 126 TC 23 Z9 28 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0915-5635 EI 1443-1661 J9 DIGEST ENDOSC JI Dig. Endosc. PD JAN PY 2014 VL 26 SU 1 SI SI BP 29 EP 42 DI 10.1111/den.12157 PG 14 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 276EQ UT WOS:000328731300004 PM 24033375 ER PT J AU Yan, TD Tian, DH LeMaire, SA Misfeld, M Elefteriades, JA Chen, EP Hughes, GC Kazui, T Griepp, RB Kouchoukos, NT Bannon, PG Underwood, MJ Mohr, FW Oo, A Sundt, TM Bavaria, JE Di Bartolomeo, R Di Eusanio, M Roselli, EE Beyersdorf, F Carrel, TP Corvera, JS Della Corte, A Ehrlich, M Hoffman, A Jakob, H Matalanis, G Numata, S Patel, HJ Pochettino, A Safi, HJ Estrera, A Perreas, KG Sinatra, R Trimarchi, S Sun, LZ Tabata, M Wang, CS Haverich, A Shrestha, M Okita, Y Coselli, J AF Yan, Tristan D. Tian, David H. LeMaire, Scott A. Misfeld, Martin Elefteriades, John A. Chen, Edward P. Hughes, G. Chad Kazui, Teruhisa Griepp, Randall B. Kouchoukos, Nicholas T. Bannon, Paul G. Underwood, Malcolm J. Mohr, Friedrich-Wilhelm Oo, Aung Sundt, Thoralf M. Bavaria, Joseph E. Di Bartolomeo, Roberto Di Eusanio, Marco Roselli, Eric E. Beyersdorf, Friedhelm Carrel, Thierry P. Corvera, Joel S. Della Corte, Alessandro Ehrlich, Marek Hoffman, Andras Jakob, Heinz Matalanis, George Numata, Satoshi Patel, Himanshu J. Pochettino, Alberto Safi, Hazim J. Estrera, Anthony Perreas, Konstantinos G. Sinatra, Riccardo Trimarchi, Santi Sun, Li-Zhong Tabata, Minoru Wang, Chunsheng Haverich, Axel Shrestha, Malakh Okita, Yutaka Coselli, Joseph TI The ARCH Projects: design and rationale (IAASSG 001) SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE Aortic arch surgery; Database; Cerebral protection ID RETROGRADE CEREBRAL PERFUSION; HYPOTHERMIC CIRCULATORY ARREST; AORTIC-ARCH; SURGERY; PROTECTION; EXPERIENCE; DISSECTION; OPERATIONS AB OBJECTIVE: A number of factors limit the effectiveness of current aortic arch studies in assessing optimal neuroprotection strategies, including insufficient patient numbers, heterogenous definitions of clinical variables, multiple technical strategies, inadequate reporting of surgical outcomes and a lack of collaborative effort. We have formed an international coalition of centres to provide more robust investigations into this topic. METHODS: High-volume aortic arch centres were identified from the literature and contacted for recruitment. A Research Steering Committee of expert arch surgeons was convened to oversee the direction of the research. RESULTS: The International Aortic Arch Surgery Study Group has been formed by 41 arch surgeons from 10 countries to better evaluate patient outcomes after aortic arch surgery. Several projects, including the establishment of a multi-institutional retrospective database, randomized controlled trials and a prospectively collected database, are currently underway. CONCLUSIONS: Such a collaborative effort will herald a turning point in the surgical management of aortic arch pathologies and will provide better powered analyses to assess the impact of varying surgical techniques on mortality and morbidity, identify predictors for neurological and operative risk, formulate and validate risk predictor models and review long-term survival outcomes and quality-of-life after arch surgery. C1 [Yan, Tristan D.; Tian, David H.; Bannon, Paul G.] Macquarie Univ, Collaborat Res CORE Grp, Sydney, NSW 2109, Australia. [Yan, Tristan D.; Bannon, Paul G.] Univ Sydney, Dept Cardiothorac Surg, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. [LeMaire, Scott A.; Coselli, Joseph] St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX USA. [LeMaire, Scott A.; Coselli, Joseph] Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Misfeld, Martin; Mohr, Friedrich-Wilhelm] Univ Leipzig, Ctr Heart, Dept Cardiac Surg, D-04109 Leipzig, Germany. [Elefteriades, John A.] Yale Univ, Sch Med, Sect Cardiac Surg, New Haven, CT USA. [Chen, Edward P.] Emory Univ, Div Cardiothorac Surg, Atlanta, GA 30322 USA. [Hughes, G. Chad] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Kazui, Teruhisa] Hokkaido Ohno Hosp, Ctr Cardiovasc, Sapporo, Hokkaido, Japan. [Griepp, Randall B.] Mt Sinai Sch Med, Dept Cardiothorac Surg, New York, NY USA. [Kouchoukos, Nicholas T.] Missouri Baptist Med Ctr, St Louis, MO USA. [Underwood, Malcolm J.] Chinese Univ Hong Kong, Div Cardiothorac Surg, Hong Kong, Hong Kong, Peoples R China. [Oo, Aung] Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Bavaria, Joseph E.] Hosp Univ Penn, Dept Cardiovasc Surg, Philadelphia, PA 19104 USA. [Di Bartolomeo, Roberto; Di Eusanio, Marco] Univ Bologna, Dept Cardiovasc Surg, St Orsola Malpighi Hosp, Bolonga, Italy. [Roselli, Eric E.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. [Beyersdorf, Friedhelm] Univ Freiburg, Dept Cardiovasc Surg, Ctr Heart, D-79106 Freiburg, Germany. [Carrel, Thierry P.] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Corvera, Joel S.] Indiana Univ Hlth Cardiovasc Surg, Methodist Hosp, Indianapolis, IN USA. [Della Corte, Alessandro] Univ Naples 2, Dept Cardiothorac Sci, Monaldi Hosp, Naples, Italy. [Ehrlich, Marek] Univ Hosp Vienna, Dept Cardiothorac Surg, Vienna, Austria. [Hoffman, Andras] Univ Hosp RWTH Aachen, Dept Cardiothorac & Vasc Surg, Aachen, Germany. [Jakob, Heinz] Univ Hosp Essen, West German Heart Ctr Essen, Dept Thorac & Cardiovasc Surg, Essen, Germany. [Jakob, Heinz] Univ Hosp Essen, West German Heart Ctr Essen, Dept Cardiol, Essen, Germany. [Matalanis, George] Austin Hlth, Dept Cardiac Surg, Melbourne, Vic, Australia. [Numata, Satoshi] Fukui Cardiovasc Ctr, Dept Cardiovasc Surg, Shinpo Fukui, Japan. [Patel, Himanshu J.] Univ Michigan, Dept Surg, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Pochettino, Alberto] Mayo Clin, Rochester, MN USA. [Safi, Hazim J.; Estrera, Anthony] Univ Texas Houston, Sch Med, Dept Cardiothorac & Vasc Surg, Mem Hermann Heart & Vasc Inst, Houston, TX USA. [Perreas, Konstantinos G.] Onassis Cardiac Surg Ctr, Dept Adult Cardiac Surg 2, Athens, Greece. [Sinatra, Riccardo] Univ Rome, Policlin St Andrea, Dept Cardiac Surg, Rome, Italy. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, Milan, Italy. [Sun, Li-Zhong] Beijing Aort Dis Ctr, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R China. [Sun, Li-Zhong] Beijing Anzhen Hosp, Beijing, Peoples R China. [Tabata, Minoru] Sakakibara Heart Inst, Tokyo, Japan. [Wang, Chunsheng] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Haverich, Axel; Shrestha, Malakh] Hannover Med Sch, Dept Cardiothorac Transplantat & Vasc Surg, Hannover, Germany. [Okita, Yutaka] Kobe Univ, Dept Surg, Grad Sch Med, Div Cardiovasc Surg, Kobe, Hyogo 657, Japan. RP Yan, TD (reprint author), Macquarie Univ, Collaborat Res CORE Grp, Sydney, NSW 2109, Australia. EM tristanyan@annalscts.com RI Trimarchi, Santi/J-7361-2016; Underwood, Malcolm John/L-6823-2016; OI Trimarchi, Santi/0000-0001-5996-3264; di bartolomeo, roberto/0000-0003-3965-5779; Della Corte, Alessandro/0000-0002-4636-3339 FU Jotec GmbH, Hechingen, Germany FX Heinz Jakob declares a financial relationship with Jotec GmbH, Hechingen, Germany. NR 25 TC 16 Z9 16 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 EI 1873-734X J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD JAN PY 2014 VL 45 IS 1 BP 10 EP 16 DI 10.1093/ejcts/ezt520 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 271JJ UT WOS:000328387600003 PM 24296985 ER PT J AU Mullegama, SV Rosenfeld, JA Orellana, C van Bon, BWM Halbach, S Repnikova, EA Brick, L Li, CM Dupuis, L Rosello, M Aradhya, S Stavropoulos, DJ Manickam, K Mitchell, E Hodge, JC Talkowski, ME Gusella, JF Keller, K Zonana, J Schwartz, S Pyatt, RE Waggoner, DJ Shaffer, LG Lin, AE de Vries, BBA Mendoza-Londono, R Elsea, SH AF Mullegama, Sureni V. Rosenfeld, Jill A. Orellana, Carmen van Bon, Bregje W. M. Halbach, Sara Repnikova, Elena A. Brick, Lauren Li, Chumei Dupuis, Lucie Rosello, Monica Aradhya, Swaroop Stavropoulos, D. James Manickam, Kandamurugu Mitchell, Elyse Hodge, Jennelle C. Talkowski, Michael E. Gusella, James F. Keller, Kory Zonana, Jonathan Schwartz, Stuart Pyatt, Robert E. Waggoner, Darrel J. Shaffer, Lisa G. Lin, Angela E. de Vries, Bert B. A. Mendoza-Londono, Roberto Elsea, Sarah H. TI Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE MBD5; gene dosage; 2q23.1; autism spectrum disorder; microduplication; microdeletion ID SMITH-MAGENIS SYNDROME; MICRODUPLICATION SYNDROMES; INTELLECTUAL DISABILITY; MICRODELETION; DIAGNOSIS; FEATURES; NETWORK AB Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein deletion or duplication results in altered gene dosage. We previously established the 2q23.1 microdeletion syndrome and report herein 23 individuals with 2q23.1 duplications, thus establishing a complementary duplication syndrome. The observed phenotype includes ID, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (pinnae anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 68 kb to 53.7 Mb, encompassing a region that includes MBD5, an important factor in methylation patterning and epigenetic regulation. We previously reported that haploinsufficiency of MBD5 is the primary causal factor in 2q23.1 microdeletion syndrome and that mutations in MBD5 are associated with autism. In this study, we demonstrate that MBD5 is the only gene in common among all duplication cases and that overexpression of MBD5 is likely responsible for the core clinical features present in 2q23.1 microduplication syndrome. Phenotypic analyses suggest that 2q23.1 duplication results in a slightly less severe phenotype than the reciprocal deletion. The features associated with a deletion, mutation or duplication of MBD5 and the gene expression changes observed support MBD5 as a dosage-sensitive gene critical for normal development. C1 [Mullegama, Sureni V.; Elsea, Sarah H.] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA USA. [Rosenfeld, Jill A.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA USA. [Orellana, Carmen; Rosello, Monica] Univ & Polytech Hosp La Fe, Serv Genet & Prenatal Diag, Valencia, Spain. [van Bon, Bregje W. M.; de Vries, Bert B. A.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Halbach, Sara; Waggoner, Darrel J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Repnikova, Elena A.; Pyatt, Robert E.] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA. [Brick, Lauren; Li, Chumei] McMaster Univ, Med Ctr, Clin Genet Program, Dept Pediat, Hamilton, ON, Canada. [Brick, Lauren; Li, Chumei] McMaster Childrens Hosp, Hamilton, ON, Canada. [Dupuis, Lucie] Hosp Sick Children, Dept Pediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Dupuis, Lucie; Mendoza-Londono, Roberto] Univ Toronto, Toronto, ON, Canada. [Aradhya, Swaroop] GeneDx, Gaithersburg, MD USA. [Stavropoulos, D. James] Hosp Sick Children, Cytogenet Lab, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. [Stavropoulos, D. James] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada. [Manickam, Kandamurugu] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA. [Mitchell, Elyse; Hodge, Jennelle C.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Mitchell, Elyse; Hodge, Jennelle C.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Talkowski, Michael E.; Gusella, James F.; Lin, Angela E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Keller, Kory; Zonana, Jonathan] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Child Dev & Rehabil Ctr, Portland, OR 97201 USA. [Schwartz, Stuart] Lab Corp Amer, Durham, NC USA. [Shaffer, Lisa G.] Genetic Vet Sci Inc, Paw Print Genet, Spokane, WA USA. [Lin, Angela E.] Massachusetts Gen Hosp Children, Boston, MA USA. [Elsea, Sarah H.] Virginia Commonwealth Univ, Sch Med, Dept Pediat, Richmond, VA USA. [Elsea, Sarah H.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Elsea, SH (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM elsea@bcm.edu RI Orellana, Carmen/B-1925-2009; Rosello, Monica/B-2319-2009; van Bon, Bregje/Q-2445-2015 OI Orellana, Carmen/0000-0003-4271-5859; Rosello, Monica/0000-0001-9234-2953; FU Fondation Jerome Lejeune FX We are thankful to all of the subjects and families involved in this study. We are grateful for the assistance of Dr Trang Le, Ms Zalak Shah, Mr Joshua Beach and Ms Jessica Webster in the collection of clinical data and in the preparation of this manuscript and to Dr Shelley Waite for neurologic evaluation of case MGH2. We thank the Fondation Jerome Lejeune (SHE) for funding portions of this study. This work was supported in part by resources from Virginia Commonwealth University and the Ramon Areces Foundation. NR 24 TC 16 Z9 16 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2014 VL 22 IS 1 BP 57 EP 63 DI 10.1038/ejhg.2013.67 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 275PP UT WOS:000328689600016 PM 23632792 ER PT J AU Liu, XD Luo, H Zhang, L Leung, FW Liu, ZG Wang, XP Huang, R Hui, N Wu, KC Fan, DM Pan, YL Guo, XG AF Liu, Xiaodong Luo, Hui Zhang, Lin Leung, Felix W. Liu, Zhiguo Wang, Xiangping Huang, Rui Hui, Na Wu, Kaichun Fan, Daiming Pan, Yanglin Guo, Xuegang TI Telephone-based re-education on the day before colonoscopy improves the quality of bowel preparation and the polyp detection rate: a prospective, colonoscopist-blinded, randomised, controlled study SO GUT LA English DT Article DE COLONOSCOPY ID SCREENING COLONOSCOPY; PATIENT EDUCATION; COLORECTAL-CANCER; DIAGNOSTIC YIELD; IMPACT; TRIAL; COLON; DETERMINES; VALIDATION; COST AB Background Despite advances in bowel preparation methods, the quality of bowel preparation in some patients undergoing colonoscopy remains unsatisfactory. The effect of telephone re-education (TRE) on the day before colonoscopy on the quality of bowel preparation and other outcome measures had not been studied. Methods A prospective colonoscopist-blinded study was conducted. All patients received regular instructions during a visit to discuss colonoscopy. Those scheduled for colonoscopy were randomly assigned to receive TRE on the day before colonoscopy (TRE group) for bowel preparation or no TRE (control group). The primary outcome was the rate of adequate bowel preparation. The secondary outcomes included polyp detection rate (PDR), non-compliance with instructions, and willingness to repeat bowel preparation. Results A total of 605 patients were randomised, 305 to the TRE group and 300 to the control group. In an intention-to-treat analysis of the primary outcome, adequate preparation was found in 81.6% vs 70.3% of TRE and control patients, respectively (p=0.001). PDR was 38.0% vs 24.7% in the TRE and control group, respectively (p<0.001). Among patients with successful colonoscopy, the Ottawa scores were 3.02.3 in the TRE group and 4.9 +/- 3.2 in the control group (p<0.001). Fewer patients who showed non-compliance with instructions were found in the TRE group (9.4% vs 32.6%, p<0.001). No significant differences were observed between the two groups with regard to willingness to have a repeat bowel preparation (p=0.409). Conclusions TRE about the details of bowel preparation on the day before colonoscopy significantly improved the quality of bowel preparation and PDR. C1 [Liu, Xiaodong; Luo, Hui; Zhang, Lin; Liu, Zhiguo; Wang, Xiangping; Huang, Rui; Hui, Na; Wu, Kaichun; Fan, Daiming; Pan, Yanglin; Guo, Xuegang] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xian 710032, Shannxi, Peoples R China. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hill, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Guo, XG (reprint author), Fourth Mil Med Univ, Xijing Hosp Digest Dis, 169 Changle West Rd, Xian 710032, Shannxi, Peoples R China. EM xuegangguo@gmail.com FU National Natural Science Foundation of China [81172288]; Science Foundation of the Ministry of Education FX We thank the nurse, Jing Li, for patient education on bowel preparation, and Subesh Kumar Dahal for preparation of the manuscript. This work was supported in part by the National Natural Science Foundation of China (81172288). Support was also received by YP from the Science Foundation of the Ministry of Education. NR 30 TC 30 Z9 33 U1 2 U2 20 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2014 VL 63 IS 1 BP 125 EP 130 DI 10.1136/gutjnl-2012-304292 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 263VB UT WOS:000327835000015 PM 23503044 ER PT J AU Wu, C Kraft, P Stolzenberg-Solomon, R Steplowski, E Brotzman, M Xu, MS Mudgal, P Amundadottir, L Arslan, AA Bueno-de-Mesquita, HB Gross, M Helzlsouer, K Jacobs, EJ Kooperberg, C Petersen, GM Zheng, W Albanes, D Boutron-Ruault, MC Buring, JE Canzian, F Cao, GW Duell, EJ Elena, JW Gaziano, JM Giovannucci, EL Hallmans, G Hutchinson, A Hunter, DJ Jenab, M Jiang, GL Khaw, KT LaCroix, A Li, ZS Mendelsohn, JB Panico, S Patel, AV Qian, ZR Riboli, E Sesso, H Shen, HB Shu, XO Tjonneland, A Tobias, GS Trichopoulos, D Virtamo, J Visvanathan, K Wactawski-Wende, J Wang, CF Yu, K Zeleniuch-Jacquotte, A Chanock, S Hoover, R Hartge, P Fuchs, CS Lin, DX Wolpin, BM AF Wu, Chen Kraft, Peter Stolzenberg-Solomon, Rachael Steplowski, Emily Brotzman, Michelle Xu, Mousheng Mudgal, Poorva Amundadottir, Laufey Arslan, Alan A. Bueno-de-Mesquita, H. Bas Gross, Myron Helzlsouer, Kathy Jacobs, Eric J. Kooperberg, Charles Petersen, Gloria M. Zheng, Wei Albanes, Demetrius Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Cao, Guangwen Duell, Eric J. Elena, Joanne W. Gaziano, J. Michael Giovannucci, Edward L. Hallmans, Goran Hutchinson, Amy Hunter, David J. Jenab, Mazda Jiang, Guoliang Khaw, Kay-Tee LaCroix, Andrea Li, Zhaoshen Mendelsohn, Julie B. Panico, Salvatore Patel, Alpa V. Qian, Zhi Rong Riboli, Elio Sesso, Howard Shen, Hongbing Shu, Xiao-Ou Tjonneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Virtamo, Jarmo Visvanathan, Kala Wactawski-Wende, Jean Wang, Chengfeng Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen Hoover, Robert Hartge, Patricia Fuchs, Charles S. Lin, Dongxin Wolpin, Brian M. TI Genome-wide association study of survival in patients with pancreatic adenocarcinoma SO GUT LA English DT Article DE Cancer Genetics; Molecular Epidemiology; Pancreatic Cancer ID MYOTUBULARIN-RELATED PROTEIN-2; LUNG-CANCER PATIENTS; DUCTAL ADENOCARCINOMA; GENE POLYMORPHISMS; RISK; SBF2; MICE; SUSCEPTIBILITY; CHEMOTHERAPY; GEMCITABINE AB Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts. C1 [Wu, Chen; Kraft, Peter; Xu, Mousheng; Mudgal, Poorva; Giovannucci, Edward L.; Hunter, David J.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China. [Wu, Chen; Wang, Chengfeng; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Stolzenberg-Solomon, Rachael; Amundadottir, Laufey; Albanes, Demetrius; Mendelsohn, Julie B.; Tobias, Geoffrey S.; Yu, Kai; Chanock, Stephen; Hoover, Robert; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Brotzman, Michelle] Westat Corp, Rockville, MD USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Helzlsouer, Kathy] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Program Biostat & Biomath, Seattle, WA 98104 USA. [Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Cao, Guangwen] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain. [Elena, Joanne W.] NCI, Div Canc Control & Populat Sci, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Fuchs, Charles S.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward L.; Fuchs, Charles S.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hutchinson, Amy] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France. [Jiang, Guoliang] Fudan Univ, Canc Hosp, Dept Radiat Oncol, Shanghai 200433, Peoples R China. [Khaw, Kay-Tee] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Clin Gerontol Unit, Cambridge CB2 2QQ, England. [LaCroix, Andrea] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Li, Zhaoshen] Second Mil Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Shanghai, Peoples R China. [Panico, Salvatore] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy. [Qian, Zhi Rong; Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Shen, Hongbing] Nanjing Med Univ, Ctr Canc, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Tjonneland, Anne] Danish Canc Soc Res Ctr, Copenhagen, Denmark. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Visvanathan, Kala] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Wang, Chengfeng] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Abdominal Surg, Beijing 100021, Peoples R China. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM lindx72@cicams.ac.cn; bwolpin@partners.org RI Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Panico, Salvatore/K-6506-2016; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Qian, Zhi rong/0000-0003-1633-4120; Panico, Salvatore/0000-0002-5498-8312; Amundadottir, Laufey/0000-0003-1859-8971; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163 FU NCI [R01CA034588, R01CA098661, P30CA016087]; National Institute of Environmental Health Sciences [ES000260]; National Heart, Lung, and Blood Institute, National Institutes of Health; US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Institutes of Health (Bethesda, MD) [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; National Cancer Institute, National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908]; American Society of Clinical Oncology Career Development Award; Howard Hughes Medical Institute Early Career Physician-Scientist Award; Lustgarten Foundation for Pancreatic Cancer Research; hanghai Men's Health Study was supported by the National Cancer Institute extramural research grant [R01 CA82729]; National Cancer Institute extramural research grant [R37 CA70867]; US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]; Intramural Research Program of the National Cancer Institute; National Institute of Aging [5U01AG018033]; National Cancer Institute [CA105069, CA73790]; Associazione Italiana per la Ricerca sul Cancro FX The NYU Women's Health Study is supported by research grants R01CA034588, R01CA098661, center grant P30CA016087 from the NCI and center grant ES000260 from the National Institute of Environmental Health Sciences. The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. PHS was supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health (Bethesda, MD). The NHS, HPFS and WHS at Harvard were supported by the National Cancer Institute, National Institutes of Health (grants P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908). BMW was supported by NCI K07 CA140790, an American Society of Clinical Oncology Career Development Award, Howard Hughes Medical Institute Early Career Physician-Scientist Award, and the Lustgarten Foundation for Pancreatic Cancer Research. The Shanghai Men's Health Study was supported by the National Cancer Institute extramural research grant (R01 CA82729). The Shanghai Women's Health Study was supported by the National Cancer Institute extramural research grant (R37 CA70867) and, partially for biological sample collection, by the Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics). PLCO was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The ATBC Study was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C from the National Cancer Institute, Department of Health and Human Services, and by funding from the Intramural Research Program of the National Cancer Institute. The coordination of EPIC is financially supported by the European Commission (DG- SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue contre le Cancer, Societe 3M, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vesterbotten (Sweden); Cancer Research UK, Medical Research Council (UK). CLUE II was supported by National Institute of Aging grant (5U01AG018033) and National Cancer Institute grants (CA105069, CA73790). We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC) for the funds that helped support the availability of the cancer registry data.; The Cancer Prevention Study II Nutrition Cohort is supported by the American Cancer Society. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government. NR 44 TC 17 Z9 18 U1 2 U2 21 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2014 VL 63 IS 1 BP 152 EP 160 DI 10.1136/gutjnl-2012-303477 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 263VB UT WOS:000327835000018 PM 23180869 ER PT J AU Ordi, J Bergeron, C Hardisson, D McCluggage, WG Hollema, H Felix, A Soslow, RA Oliva, E Tavassoli, FA Alvarado-Cabrero, I Wells, M Nogales, FF AF Ordi, Jaume Bergeron, Christine Hardisson, David McCluggage, W. Glenn Hollema, Harry Felix, Ana Soslow, Robert A. Oliva, Esther Tavassoli, Fattaneh A. Alvarado-Cabrero, Isabel Wells, Michael Nogales, Francisco F. TI Reproducibility of current classifications of endometrial endometrioid glandular proliferations: further evidence supporting a simplified classification SO HISTOPATHOLOGY LA English DT Article DE endometrial carcinoma; endometrial hyperplasia; interobserver variability ID LONG-TERM; HYPERPLASIA; DIAGNOSIS; HISTOPATHOLOGY; PREDICTION; BIOPSY AB AimsTo compare the reproducibility of the current (2003) World Health Organization (WHO), endometrial intraepithelial neoplasia (EIN) and European Working Group (EWG) classifications of endometrial endometrioid proliferations. Methods and resultsNine expert gynaecological pathologists from Europe and North America reviewed 198 endometrial biopsy/curettage specimens originally diagnosed as low-grade lesions. All observers were asked to classify the cases by using the categories described in each scheme: six for WHO, four for EIN, and three for EWG. The results were evaluated by kappa statistics for more than two observations. The analysis was repeated using only two major categories (benign versus atypical/carcinoma). Both the WHO and EIN classifications showed poor interobserver agreement (=0.337 and =0.419, respectively), whereas the EWG classification showed moderate agreement (=0.530). Full agreement between pathologists occurred in only 28% for the WHO classification, 39% for the EIN classification, and 59% for the EWG classification. With only two diagnostic categories, kappa values increased in all classifications, but only the EWG classification reached a substantial level of agreement (=0.621); similarly, full agreement among all pathologists increased to 70% for the WHO classification, 69% for the EIN classification, and 72% for the EWG classification. ConclusionsA two-tier classification of endometrial endometrioid proliferative lesions improves reproducibility, and should be considered for the diagnosis of endometrial biopsy/curettage specimens. C1 [Ordi, Jaume] Univ Barcelona, Fac Med, Dept Pathol, CRESIB Ctr Recerca Salut Int Barcelona,Hosp Clin, Barcelona 7, Spain. [Bergeron, Christine] Lab CERBA, St Ouen, France. [Hardisson, David] Autonomous Univ Madrid, Dept Pathol, Hosp La Paz, IdiPAZ,Inst Hlth Res, E-28049 Madrid, Spain. [McCluggage, W. Glenn] Royal Grp Hosp, Dept Pathol, Belfast, Antrim, North Ireland. [Hollema, Harry] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands. [Felix, Ana] Inst Oncol, Dept Pathol, Lisbon, Portugal. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tavassoli, Fattaneh A.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Alvarado-Cabrero, Isabel] Hosp Star Med, Dept Pathol, Santa Fe, Mexico. [Wells, Michael] Univ Sheffield, Dept Oncol, Sheffield, S Yorkshire, England. [Nogales, Francisco F.] Univ Granada, Dept Pathol, Granada 18012, Spain. RP Nogales, FF (reprint author), Univ Granada, Fac Med, Dept Pathol, Av Madrid 11, Granada 18012, Spain. EM fnogales@ugr.es RI Hardisson, David/E-2832-2010; OI Hardisson, David/0000-0002-2183-3699; Soslow, Robert/0000-0002-7269-5898; Felix, Ana/0000-0002-2653-2262 NR 18 TC 4 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD JAN PY 2014 VL 64 IS 2 BP 284 EP 292 DI 10.1111/his.12249 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 270VR UT WOS:000328347800011 PM 24111732 ER PT J AU Garland, DL Fernandez-Godino, R Kaur, I Speicher, KD Harnly, JM Lambris, JD Speicher, DW Pierce, EA AF Garland, Donita L. Fernandez-Godino, Rosario Kaur, Inderjeet Speicher, Kaye D. Harnly, James M. Lambris, John D. Speicher, David W. Pierce, Eric A. TI Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration SO HUMAN MOLECULAR GENETICS LA English DT Article ID AGE-RELATED MACULOPATHY; SORSBYS FUNDUS DYSTROPHY; EXTRACELLULAR-MATRIX PROTEINS; PRINCIPAL COMPONENT ANALYSIS; ONSET RETINAL DEGENERATION; BASAL LAMINAR DEPOSIT; FACTOR-H POLYMORPHISM; DRUSEN FORMATION; PIGMENT-EPITHELIUM; BRUCHS MEMBRANE AB Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1(R345W/R345W) mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1(R345W/R345W) mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1(R345W/R345W):C3(-/-) double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations. C1 [Garland, Donita L.; Fernandez-Godino, Rosario; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, Boston, MA 02114 USA. [Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA 02114 USA. [Kaur, Inderjeet] LV Prasad Eye Inst, Kallam Anji Reddy Mol Genet Lab, Hyderabad, Andhra Pradesh, India. [Speicher, Kaye D.; Speicher, David W.] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, Philadelphia, PA 19104 USA. [Speicher, Kaye D.; Speicher, David W.] Wistar Inst Anat & Biol, Mol Oncogenesis Program, Philadelphia, PA 19104 USA. [Harnly, James M.] USDA, Food Composit & Methods Dev Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. [Lambris, John D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. RP Garland, DL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM donita_garland@meei.harvard.edu; eric_pierce@meei.harvard.edu OI Lambris, John/0000-0002-9370-5776; Pierce, Eric/0000-0002-2354-4102 FU Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA; Rosanne Silbermann Foundation; National Cancer Institute (NCI Cancer Core Grant) [CA010815]; National Eye Institute (MEEI Core Grant) [P30 EY014104]; National Institutes of Health [AI068730, EY020633] FX This work was supported by the Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114; the Rosanne Silbermann Foundation; the National Cancer Institute (NCI Cancer Core Grant CA010815 to The Wistar Institute); the National Eye Institute (MEEI Core Grant P30 EY014104) and the National Institutes of Health (AI068730 and EY020633 to J.D.L.). NR 128 TC 11 Z9 11 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2014 VL 23 IS 1 BP 52 EP 68 DI 10.1093/hmg/ddt395 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 272SZ UT WOS:000328482300005 PM 23943789 ER PT J AU Stewart, CJR Ardakani, NM Doherty, DA Young, RH AF Stewart, Colin J. R. Ardakani, Nima M. Doherty, Dorota A. Young, Robert H. TI An Evaluation of the Morphologic Features of Low-grade Mucinous Neoplasms of the Appendix Metastatic in the Ovary, and Comparison With Primary Ovarian Mucinous Tumors SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Ovary; Mucinous tumor; Borderline; Appendix; Teratoma; LAMN ID MATURE CYSTIC TERATOMA; PSEUDOMYXOMA-PERITONEI; CLINICOPATHOLOGICAL ANALYSIS; IMMUNOHISTOCHEMICAL EXPRESSION; INTRAOPERATIVE CONSULTATION; EPITHELIAL NEOPLASMS; ORIGIN; CARCINOMAS; PATHOLOGY; EMPHASIS AB It may be difficult to distinguish ovarian involvement by a low-grade appendiceal mucinous neoplasm (LAMN) from a primary gastrointestinal-type primary borderline (proliferative) ovarian tumor (IBMT) or an ovarian mucinous tumor arising within a teratoma, particularly when the latter is associated with mucinous ascites/pseudomyxoma peritonei. We noted that LAMNs involving the ovaries show 2 distinctive histologic features, scalloped glands and subepthelial stromal clefts, whereas IBMTs more often are associated with reactive cellular stroma and histiocyte aggregates (mucin granulomas). The frequency of these features was investigated in 18 LAMNs (16 with pseudomyxoma peritonei), 18 primary IBMTs, and 6 teratoma-associated mucinous tumors (selected on the basis of associated pseudomyxoma peritonei). Scalloped glands and subepithelial clefts were identified in 17 and 16 LAMNs, respectively, and in 3 and 7 IBMTs, respectively. Conversely, reactive stroma and histiocyte aggregates were present in 2 and 0 LAMNs, respectively, and in 11 and 10 IBMTs, respectively. LAMNs were often bilateral (12/18 cases) and they more frequently showed mucin dissection of the ovarian stroma and tall mucin-rich (hypermucinous) epithelial cells compared with IBMTs. Our findings suggest that scalloped glands, subepithelial clefts, cellular stroma, and histiocyte aggregates may be useful additional morphologic parameters to help distinguish these tumor types. However, teratoma-associated mucinous neoplasms can show identical histologic features to those of LAMNs involving the ovary, and therefore accurate diagnosis of such cases requires careful macroscopic and microscopic examinations of the ovaries together with complete histologic assessment of the appendix. C1 [Stewart, Colin J. R.; Ardakani, Nima M.] King Edward Mem Hosp Women, Dept Histopathol, Perth, WA 6008, Australia. [Stewart, Colin J. R.; Doherty, Dorota A.] Univ Western Australia, Sch Womens & Infants Hlth, Nedlands, WA 6009, Australia. [Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Boston, MA USA. RP Stewart, CJR (reprint author), King Edward Mem Hosp Women, Dept Histopathol, Bagot Rd, Perth, WA 6008, Australia. EM colin.stewart@health.wa.gov.au NR 45 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2014 VL 33 IS 1 BP 1 EP 10 DI 10.1097/PGP.0b013e318284e070 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 274CL UT WOS:000328582600001 PM 24300528 ER PT J AU Volpicelli, ER Lezcano, C Zhan, Q Girouard, SD Kindelberger, DW Frank, MH Frank, NY Crum, CP Murphy, GF AF Volpicelli, Elgida R. Lezcano, Cecilia Zhan, Qian Girouard, Sasha D. Kindelberger, David W. Frank, Markus H. Frank, Natasha Y. Crum, Christopher P. Murphy, George F. TI The Multidrug-Resistance Transporter ABCB5 is Expressed in Human Placenta SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Stem cell; Trophoblast; Syncytiotrophoblast; Cytotrophoblast; MDR transporter; ABCB5 ID P-GLYCOPROTEIN; MALIGNANT-MELANOMA; STEM-CELLS; LOCALIZATION; TERM AB ATP-binding cassette (ABC) transporters in placenta protectively transport drugs and xenobiotics. ABCB5 [subfamily B (MDR/TAP)] is a novel ABC multidrug-resistance transporter that also mediates cell fusion, stem cell function, and vasculogenic plasticity. Immunohistochemistry and double-labeling immunofluorescence staining for ABCB5 and ABCB5/CD200, respectively, was performed on formalin-fixed, paraffin-embedded placental tissue from 5 first trimester, 5 second trimester, and 5 term pregnancies as well as 5 partial moles, and 5 complete moles. In addition, tumor cells from 5 choriocarcinoma and 5 placental site trophoblastic tumor cases were examined. ABCB5 staining was observed in villous trophoblasts in 100% (5/5) of first trimester placentas (with progressive decrease in term placentas); 100% of partial moles (5/5); and 100% of complete moles (5/5). Notably, reactivity was discretely restricted to the inner trophoblast layer, with no staining of overlying syncytiotrophoblast. Antibody specificity and localization was confirmed further by in situ hybridization. ABCB5 expression was retained in 20% of choriocarcinomas (1/5) and 40% of placental site trophoblastic tumors (2/5). Prior studies have localized expression of multidrug-resistance-1, also known as ABCB1, within the syncytiotrophoblast of early placentas, where it serves a protective function as an efflux transporter. Our results show that ABCB5 is preferentially expressed in the cytotrophoblast layer of placental villi. The expression of this novel biomarker at the maternal-fetal interface raises questions on its role in placental structure and function as well as on its potential contribution to the protective efflux provided by other P-glycoprotein transporters. C1 [Volpicelli, Elgida R.; Lezcano, Cecilia; Zhan, Qian; Crum, Christopher P.; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Girouard, Sasha D.; Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Volpicelli, Elgida R.; Lezcano, Cecilia; Zhan, Qian; Girouard, Sasha D.; Frank, Markus H.; Frank, Natasha Y.; Crum, Christopher P.; Murphy, George F.] Harvard Univ, Sch Med, Boston, MA USA. [Frank, Markus H.; Frank, Natasha Y.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Jamaica Plain, MA USA. RP Murphy, GF (reprint author), Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave,EBRC 401, Boston, MA 02115 USA. EM gmurphy@rics.bwh.harvard.edu RI Frank, Markus/O-1625-2014 OI Frank, Markus/0000-0002-1312-0488 FU U.S. Department of Veterans Affairs: BLR&D VA Merit Award [10688354]; [NIH: P50 CA93683]; [P30 AR42689]; [R01138231]; [R01CA158467]; [R01CA113796] FX This work was in part supported by the following Grants from the NIH: P50 CA93683, P30 AR42689, R01138231, R01CA158467, and R01CA113796, and the U.S. Department of Veterans Affairs: BLR&D VA Merit Award 10688354. NR 23 TC 5 Z9 5 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2014 VL 33 IS 1 BP 45 EP 51 DI 10.1097/PGP.0b013e31829c677f PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 274CL UT WOS:000328582600008 PM 24300535 ER PT J AU Melikian, GL Rhee, SY Varghese, V Porter, D White, K Taylor, J Towner, W Troia, P Burack, J DeJesus, E Robbins, GK Razzeca, K Kagan, R Liu, TF Fessel, WJ Israelski, D Shafer, RW AF Melikian, George L. Rhee, Soo-Yon Varghese, Vici Porter, Danielle White, Kirsten Taylor, Jonathan Towner, William Troia, Paolo Burack, Jeffrey DeJesus, Edwin Robbins, Gregory K. Razzeca, Kristin Kagan, Ron Liu, Tommy F. Fessel, W. Jeffrey Israelski, Dennis Shafer, Robert W. TI Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE HIV-1; drug resistance; linear regression; etravirine; rilpivirine ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXPERIENCED HIV-1-INFECTED PATIENTS; AMINO-ACID SUBSTITUTIONS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; VIROLOGICAL FAILURE; CONFER RESISTANCE; TMC125 ETRAVIRINE; HIV-1; MUTATIONS AB Objectives: The introduction of two new non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the past 5 years and the identification of novel NNRTI-associated mutations have made it necessary to reassess the extent of phenotypic NNRTI cross-resistance. Methods: We analysed a dataset containing 1975, 1967, 519 and 187 genotype-phenotype correlations for nevirapine, efavirenz, etravirine and rilpivirine, respectively. We used linear regression to estimate the effects of RT mutations on susceptibility to each of these NNRTIs. Results: Sixteen mutations at 10 positions were significantly associated with the greatest contribution to reduced phenotypic susceptibility (>= 10-fold) to one or more NNRTIs, including: 14 mutations at six positions for nevirapine (K101P, K103N/S, V106A/M, Y181C/I/V, Y188C/L and G190A/E/Q/S); 10 mutations at six positions for efavirenz (L100I, K101P, K103N, V106M, Y188C/L and G190A/E/Q/S); 5 mutations at four positions for etravirine (K101P, Y181I/V, G190E and F227C); and 6 mutations at five positions for rilpivirine (L100I, K101P, Y181I/V, G190E and F227C). G190E, a mutation that causes high-level nevirapine and efavirenz resistance, also markedly reduced susceptibility to etravirine and rilpivirine. K101H, E138G, V179F and M230L mutations, associated with reduced susceptibility to etravirine and rilpivirine, were also associated with reduced susceptibility to nevirapine and/or efavirenz. Conclusions: The identification of novel cross-resistance patterns among approved NNRTIs illustrates the need fora systematic approach for testing novel NNRTIs against clinical virus isolates with major NNRTI-resistance mutations and for testing older NNRTIs against virus isolates with mutations identified during the evaluation of a novel NNRTI. C1 [Melikian, George L.; Rhee, Soo-Yon; Varghese, Vici; Liu, Tommy F.; Israelski, Dennis; Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Porter, Danielle; White, Kirsten] Gilead Sci, Foster City, CA USA. [Taylor, Jonathan] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Towner, William] Kaiser Permanente Med Care Program, Dept Med, Los Angeles, CA USA. [Troia, Paolo] UC Davis Med Ctr, Div Infect Dis, Davis, CA USA. [Burack, Jeffrey] Alta Bates Summit Med Ctr, East Bay AIDS Ctr, Oakland, CA USA. [DeJesus, Edwin] Orlando Immunol Ctr, Orlando, FL USA. [Robbins, Gregory K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Robbins, Gregory K.] Harvard Univ, Sch Med, Boston, MA USA. [Razzeca, Kristin] Palo Alto Med Fdn, Palo Alto, CA USA. [Kagan, Ron] Quest Diagnost, San Juan Capistrano, CA USA. [Fessel, W. Jeffrey] Kaiser Permanente Med Care Program Northern Calif, San Francisco, CA USA. RP Rhee, SY (reprint author), Stanford Univ, Dept Med, Stanford, CA 94305 USA. EM syrhee@stanford.edu FU NIAID at NIH [AI068581] FX This work was supported by NIAID at NIH (AI068581: 'Public HIV Drug Resistance Database' to S.-Y. R., T. F. L. and R. W. S.). NR 36 TC 25 Z9 28 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JAN PY 2014 VL 69 IS 1 BP 12 EP 20 DI 10.1093/jac/dkt316 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 271XR UT WOS:000328425400002 PM 23934770 ER PT J AU Boyd, JD Lee-Armandt, JP Feiler, MS Zaarur, N Liu, M Kraemer, B Concannon, JB Ebata, A Wolozin, B Glicksman, MA AF Boyd, Justin D. Lee-Armandt, J. Peter Feiler, Marisa S. Zaarur, Nava Liu, Min Kraemer, Brian Concannon, John B. Ebata, Atsushi Wolozin, Benjamin Glicksman, Marcie A. TI A High-Content Screen Identifies Novel Compounds That Inhibit Stress-Induced TDP-43 Cellular Aggregation and Associated Cytotoxicity SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE amyotrophic lateral sclerosis; RNA granule; RNA binding protein; aggregation; high-throughput screen; protein synthesis ID AMYOTROPHIC-LATERAL-SCLEROSIS; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; RNA TRIAGE; GRANULES; PROTEIN; NEURODEGENERATION; PROTEINOPATHIES; DEGENERATION; MUTATION AB TDP-43 is an RNA binding protein found to accumulate in the cytoplasm of brain and spinal cord from patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Nuclear TDP-43 protein regulates transcription through several mechanisms, and under stressed conditions, it forms cytoplasmic aggregates that co-localize with stress granule (SG) proteins in cell culture. These granules are also found in the brain and spinal cord of patients affected with ALS and FTLD. The mechanism through which TDP-43 might contribute to neurodegenerative diseases is poorly understood. To investigate the pathophysiology of TDP-43 aggregation and to isolate potential therapeutic targets, we screened a chemical library of 75,000 compounds using high-content analysis with PC12 cells that inducibly express human TDP-43 tagged with green fluorescent protein (GFP). The screen identified 16 compounds that dose-dependently decreased the TDP-43 inclusions without significant cellular toxicity or changes in total TDP-43 expression levels. To validate the effect, we tested compounds by Western blot analysis and in a Caenorhabditis elegans model that replicates some of the relevant disease phenotypes. The hits from this assay will be useful for elucidating regulation of TDP-43, stress granule response, and possible ALS therapeutics. C1 [Boyd, Justin D.; Liu, Min; Concannon, John B.; Glicksman, Marcie A.] Brigham & Womens Hosp, Harvard NeuroDiscovery Ctr, Lab Drug Discovery Neurodegenerat, Cambridge, MA USA. [Boyd, Justin D.; Liu, Min; Concannon, John B.; Glicksman, Marcie A.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Lee-Armandt, J. Peter; Feiler, Marisa S.; Zaarur, Nava; Ebata, Atsushi; Wolozin, Benjamin] Boston Univ, Dept Pharmacol & Expt Therapeut, Boston, MA 02215 USA. [Kraemer, Brian] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kraemer, Brian] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98104 USA. [Ebata, Atsushi] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Wolozin, Benjamin] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Glicksman, MA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, 65 Landsdowne St, Cambridge, MA 02139 USA. EM bwolozin@bu.edu; mglicksman@rics.bwh.harvard.edu OI Ebata, Atsushi/0000-0001-9051-2971 FU National Institutes of Health [NIH] [ES020395, NS066108, NS073679, NS060872]; BrightFocus Foundation; NIH [NS073679]; ALS Therapy Alliance; Harvard NeuroDiscovery Center; Department of Veterans Affairs [1147891]; National Institutes of Health [R01NS064131] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grant awards to BW (National Institutes of Health [NIH] grants ES020395, NS066108, NS073679, NS060872, and BrightFocus Foundation) and to MAG (NIH NS073679, ALS Therapy Alliance and the Harvard NeuroDiscovery Center). This work was supported by grants from the Department of Veterans Affairs to BK (Merit Review Grant #1147891) and National Institutes of Health (R01NS064131). NR 28 TC 10 Z9 11 U1 0 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD JAN PY 2014 VL 19 IS 1 SI SI BP 44 EP 56 DI 10.1177/1087057113501553 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 272GC UT WOS:000328447300004 PM 24019256 ER PT J AU Doherty, AL Battaglino, RA Donovan, J Gagnon, D Lazzari, AA Garshick, E Zafonte, R Morse, LR AF Doherty, Ashley L. Battaglino, Ricardo A. Donovan, Jayne Gagnon, David Lazzari, Antonio A. Garshick, Eric Zafonte, Ross Morse, Leslie R. TI Adiponectin Is a Candidate Biomarker of Lower Extremity Bone Density in Men With Chronic Spinal Cord Injury SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOPOROSIS; ADIPONECTIN; BIOMARKER; SPINAL CORD INJURY; REHABILITATION MEDICINE ID SYMPATHETIC-NERVOUS-SYSTEM; RESTING METABOLIC-RATE; BODY-MASS INDEX; MINERAL DENSITY; SERUM LEPTIN; POSTMENOPAUSAL WOMEN; PLASMA LEPTIN; ELDERLY-MEN; FAT MASS; OSTEOBLAST DIFFERENTIATION AB Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation. (c) 2014 American Society for Bone and Mineral Research. C1 [Doherty, Ashley L.; Donovan, Jayne; Zafonte, Ross; Morse, Leslie R.] Spaulding Rehabil Hosp, Spaulding Harvard Spinal Cord Injury SCI Model Sy, Boston, MA USA. [Battaglino, Ricardo A.; Morse, Leslie R.] Forsyth Inst, Cambridge, MA USA. [Battaglino, Ricardo A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Gagnon, David] Boston Univ, Sch Publ Hlth, Dept Biostat, VA Cooperat Studies Program,VA Boston Healthcare, Boston, MA USA. [Lazzari, Antonio A.] VA Boston Healthcare Syst, Primary Care Sect, Boston, MA USA. [Lazzari, Antonio A.] VA Boston Healthcare Syst, Rheumatol Sect, Boston, MA USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Zafonte, Ross; Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. RP Morse, LR (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Harvard SCI Model Syst,Dept PMR, 300 1st Ave, Charlestown, MA 02129 USA. EM lmorse4@partners.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Institute of Child Health and Human Development [R21HD057030, R21HD057030-02S1]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270-01]; Department of Education, NIDRR [H133N110010]; Office of Research and Development, Rehabilitation Research and Development (Merit Review Grant) [B6618R]; Massachusetts Veterans Epidemiology Research and Information Center, Cooperative Studies Program, Department of Veterans Affairs FX This work was supported by the National Institute of Child Health and Human Development (R21HD057030 and R21HD057030-02S1), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01AR059270-01), the Department of Education, NIDRR (H133N110010), the Office of Research and Development, Rehabilitation Research and Development (Merit Review Grant B6618R), and the Massachusetts Veterans Epidemiology Research and Information Center, Cooperative Studies Program, Department of Veterans Affairs. We thank Sam Davis, clinical research coordinator and technician, Boston VA Healthcare System, for assisting with bone density scans; and Rachael Burns and Kara Loo, research assistants, Boston VA Healthcare System, for collection of anthropometric data. NR 59 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2014 VL 29 IS 1 BP 251 EP 259 DI 10.1002/jbmr.2020 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 274HS UT WOS:000328598000025 PM 23787489 ER PT J AU Gupta, NK Yilmaz, O Fisher, M Yajnik, V AF Gupta, Nitin K. Yilmaz, Omer Fisher, Mark Yajnik, Vijay TI Abatacept A New Treatment Option for Refractory Adult Autoimmune Enteropathy SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE autoimmune enteropathy; enteritis; abatacept; diarrhea ID DISEASE; GUT AB Autoimmune enteropathy (AIE) is a rare disease that has been observed in both children and adults. It typically manifests with symptoms of diarrhea, requiring long-term immunosuppression. Endoscopically, the duodenum typically exhibits villous blunting with partial or complete villous blunting, deep crypt lymphocytosis, increased apoptotic bodies, and minimal intraepithelial lymphocytosis on histologic analysis. The pathophysiology of AIE likely involves a hyperactive immune state in the setting of a T-cell regulatory defect, resulting in destruction of the enterocyte. We report a case of a 49-year-old woman who presented with refractory diarrhea, diagnosed as AIE. After failing multiple conventional therapies, she demonstrated clinical and histologic response to abatacept, a selective modulator of T-cell activation. We aim to increase awareness of this rare inflammatory disorder and new treatment options for this debilitating condition. C1 [Gupta, Nitin K.; Yajnik, Vijay] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Yilmaz, Omer] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. [Fisher, Mark] Massachusetts Gen Hosp, Dept Rheumatol, Allergy & Immunol Div, Boston, MA 02114 USA. RP Yajnik, V (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM vyajnik@partners.org RI Gupta, Nitin/A-1076-2016 OI Gupta, Nitin/0000-0002-4471-2363 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [T32DK007191] FX N.K.G. supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number T32DK007191. M.F. has an investigator initiated support from Novartis. NR 12 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JAN PY 2014 VL 48 IS 1 BP 55 EP 58 DI 10.1097/MCG.0b013e3182a4e0ec PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 274UA UT WOS:000328630500012 PM 24045285 ER PT J AU Johnson, HM Thorpe, CT Bartels, CM Schumacher, JR Palta, M Pandhi, N Sheehy, AM Smith, MA AF Johnson, Heather M. Thorpe, Carolyn T. Bartels, Christie M. Schumacher, Jessica R. Palta, Mari Pandhi, Nancy Sheehy, Ann M. Smith, Maureen A. TI Undiagnosed hypertension among young adults with regular primary care use SO JOURNAL OF HYPERTENSION LA English DT Article DE delayed diagnosis; hypertension; young adults ID AMERICAN-HEART-ASSOCIATION; CHRONIC KIDNEY-DISEASE; HIGH BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR-DISEASE; DIABETES CARE; TRENDS; POPULATION; PREVALENCE; IMPACT AB Objective:Young adults meeting hypertension diagnostic criteria have a lower prevalence of a hypertension diagnosis than middle-aged and older adults. The purpose of this study was to compare the rates of a new hypertension diagnosis for different age groups and identify predictors of delays in the initial diagnosis among young adults who regularly use primary care.Methods:A 4-year retrospective analysis included 14970 patients, at least 18 years old, who met clinical criteria for an initial hypertension diagnosis in a large, Midwestern, academic practice from 2008 to 2011. Patients with a previous hypertension diagnosis or prior antihypertensive medication prescription were excluded. The probability of diagnosis at specific time points was estimated by Kaplan-Meier analysis. Cox proportional hazard models (hazard ratio; 95% confidence interval) were fit to identify predictors of delays to an initial diagnosis, with a subsequent subset analysis for young adults (18-39 years old).Results:After 4 years, 56% of 18-24-year-olds received a diagnosis compared with 62% (25-31-year-olds), 68% (32-39-year-olds), and more than 70% (40-year-olds). After adjustment, 18-31-year-olds had a 33% slower rate of receiving a diagnosis (18-24 years hazard ratio 0.66, 0.53-0.83; 25-31 years hazard ratio 0.68, 0.58-0.79) compared with adults at least 60 years. Other predictors of a slower diagnosis rate among young adults were current tobacco use, white ethnicity, and non-English primary language. Young adults with diabetes, higher blood pressures, or a female provider had a faster diagnosis rate.Conclusion:Provider and patient factors are critical determinants of poor hypertension diagnosis rates among young adults with regular primary care use. C1 [Johnson, Heather M.; Bartels, Christie M.; Sheehy, Ann M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA. [Johnson, Heather M.; Bartels, Christie M.; Schumacher, Jessica R.; Pandhi, Nancy; Sheehy, Ann M.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Madison, WI USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Schumacher, Jessica R.; Palta, Mari; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Palta, Mari] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. RP Johnson, HM (reprint author), Div Cardiovasc Med, H4-512 CSC,MC 3248,600 Highland Ave, Madison, WI 53792 USA. EM hm2@medicine.wisc.edu OI Johnson, Heather/0000-0002-4916-3519 FU Clinical and Translational Science Award (CTSA) program; National Center for Research Resources (NCRR) [UL1RR025011]; National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health [U54TR000021]; National Heart, Lung, and Blood Institute of the National Institutes of Health [K23HL112907]; University of Wisconsin Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [K23AR062381]; National Institute on Aging of the National Institutes of Health [K08AG029527]; University of Wisconsin Health Innovation Program; University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program FX Research reported in this study was supported by the Clinical and Translational Science Award (CTSA) program, previously through the National Center for Research Resources (NCRR) under award number UL1RR025011, and now by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health under award number U54TR000021. H.J. is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL112907, and also by the University of Wisconsin Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health. C.B. is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR062381. N.P. is supported by the National Institute on Aging of the National Institutes of Health under award number K08AG029527. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Additional funding for this project was provided by the University of Wisconsin Health Innovation Program and the University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program.; Additional funding for this project was provided by the University of Wisconsin Health Innovation Program and the University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program. NR 42 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2014 VL 32 IS 1 BP 65 EP 74 DI 10.1097/HJH.0000000000000008 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 276IK UT WOS:000328743500010 PM 24126711 ER PT J AU Roider, EM Fisher, DE AF Roider, Elisabeth M. Fisher, David E. TI The Impact of MITF on Melanoma Development: News from Bench and Bedside SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID GERMLINE MUTATION; CANCER; FAMILY; PREDISPOSES; SUMOYLATION; EXPRESSION; LINEAGE AB In the current issue, two articles highlight the impact of melanocyte transcription factor (MITF) on melanoma development. In the first, Lister et al reveal in vivo proof of MITF directly regulating tumor development in BRAF(V600E) melanomas. In the second, Sturm et al present a clinical trial that emphasizes the importance of the recently discovered E318K MITF germline mutation in patients with multiple primary melanomas. C1 [Roider, Elisabeth M.; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 12 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2014 VL 134 IS 1 BP 16 EP 17 DI 10.1038/jid.2013.390 PG 2 WC Dermatology SC Dermatology GA 274GE UT WOS:000328594000006 PM 24352080 ER PT J AU Mao, XM Li, H Sano, Y Gaestel, M Park, JM Payne, AS AF Mao, Xuming Li, Hong Sano, Yasuyo Gaestel, Matthias Park, Jin Mo Payne, Aimee S. TI MAPKAP Kinase 2 (MK2)-Dependent and -Independent Models of Blister Formation in Pemphigus Vulgaris SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; P38 MAPK; PHOSPHORYLATION; DESMOGLEIN-3; INHIBITION; P38MAPK; SKIN; AUTOANTIBODIES; MK2; BIOSYNTHESIS AB Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by autoantibodies to the keratinocyte adhesion protein desmoglein 3 (Dsg3). Previous studies suggest that PV pathogenesis involves p38 mitogen-activated protein kinase-dependent and -independent pathways. However, p38 is a difficult protein to study and therapeutically target because it has four isoforms and multiple downstream effectors. In this study, we identify MAPKAP (mitogen-activated protein kinase-activated protein) kinase 2 (MK2) as a downstream effector Of p38 signaling in PV and describe MK2-dependent and -independent mechanisms of blister formation using passive transfer of human anti-Dsg IgG4 mAbs to neonatal mice. In human keratinocytes, PV mAbs activate MK2 in a dose-dependent manner. MK2 is also activated in human pemphigus skin blisters, causing translocation of MK2 from the nucleus to the cytosol. Small-molecule inhibition of MK2 and silencing of MK2 expression block PV mAb-induced Dsg3 endocytosis in human keratinocytes. In addition, small-molecule inhibition and genetic deletion of p38 alpha, and MK2 inhibit spontaneous but not induced suprabasal blisters by PV mAbs in mouse passive transfer models. Collectively, these data suggest that MK2 is a key downstream effector of p38 that can modulate PV autoantibody pathogenicity. MK2 inhibition may be a valuable adjunctive therapy for control of pemphigus blistering. C1 [Mao, Xuming; Li, Hong; Payne, Aimee S.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Sano, Yasuyo; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Sano, Yasuyo; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA USA. [Gaestel, Matthias] Hannover Med Sch, Inst Biochem, Hannover, Germany. RP Payne, AS (reprint author), Univ Penn, Dept Dermatol, 217A Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. EM paynea@mail.med.upenn.edu OI Gaestel, Matthias/0000-0002-4944-4652 FU NIAID NIH HHS [AI074957, R01 AI074957]; NIAMS NIH HHS [R01 AR057001, AR053505, AR057001, AR057217, K08 AR053505, P30 AR057217] NR 31 TC 16 Z9 14 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2014 VL 134 IS 1 BP 68 EP 76 DI 10.1038/jid.2013.224 PG 9 WC Dermatology SC Dermatology GA 274GE UT WOS:000328594000013 PM 23657501 ER PT J AU Kibbe, MR Sarr, MG Livingston, EH Freischlag, JA Lillemoe, KD McFadden, DW AF Kibbe, Melina R. Sarr, Michael G. Livingston, Edward H. Freischlag, Julie A. Lillemoe, Keith D. McFadden, David W. TI The Art and Science of Publishing: Reflections from Editors of Surgery Journals. Association for Academic Surgery 2013 Presidential Session SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 8th Annual Academic Surgical Congress CY FEB 05-07, 2013 CL New Orleans, LA SP Assoc Acad Surg, Soc Univ Surg ID PUBLICATION; APPLICANTS AB During the 8th Annual Academic Surgical Congress held in New Orleans, Louisiana, on February 5-7, 2013, the Association for Academic Surgery (AAS) Presidential Session was dedicated to the topic of publishing. A survey consisting of 37 questions on issues related to publishing was administered to the AAS membership 1 mo before the meeting. The results of the survey were then presented during the 2013 AAS Presidential Session. In addition, a panel of five editors from surgery journals relevant to the membership of the AAS was convened to discuss topics addressed in the results of the survey. These topics included: (1) how to publish in high-impact factor journals; (2) top five reasons why manuscripts get rejected; (3) the do's and don'ts of publishing (i.e., ethics of publishing); (4) how to get on an editorial board; and (5) the future of publishing. This review summarizes the contents of this AAS Presidential Session and provides information relevant for any academician, investigator, or scientist. Published by Elsevier Inc. C1 [Kibbe, Melina R.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Sarr, Michael G.] Mayo Clin, Dept Surg, Rochester, MN USA. [Livingston, Edward H.] Univ Texas Arlington, SW Med Sch, Dept Surg & Biomed Engn, Arlington, TX 76019 USA. [Livingston, Edward H.] Univ Texas Arlington, Arlington, TX 76019 USA. [Freischlag, Julie A.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [McFadden, David W.] Univ Connecticut, Dept Surg, Farmington, CT USA. RP Kibbe, MR (reprint author), Div Vasc Surg, 676 N St Clair St,Suite 650, Chicago, IL 60611 USA. EM mkibbe@nmh.org NR 12 TC 3 Z9 3 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2014 VL 186 IS 1 BP 7 EP 15 DI 10.1016/j.jss.2013.08.002 PG 9 WC Surgery SC Surgery GA 274TJ UT WOS:000328628800002 PM 24035228 ER PT J AU Yeh, DD Hwabejire, JO DeMoya, MA Alam, HB King, DR Velmahos, GC AF Yeh, D. Dante Hwabejire, John O. DeMoya, Marc A. Alam, Hasan B. King, David R. Velmahos, George C. TI Sternal fracture-an analysis of the National Trauma Data Bank SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Sternal fracture; NTDB; Motor vehicle crash; Blunt cardiac injury ID INJURIES; MANAGEMENT; BLUNT AB Background: The clinical significance of sternal fractures (SFs) after blunt trauma is heavily debated. We aimed to test the hypothesis that isolated SF is not associated with significant morbidity or mortality. Materials and methods: The National Trauma Data Bank (NTDB) sets for 2007-2010 were retrospectively examined. Adult subjects with SF were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Data collected included demographics, mechanisms of injury, clinical variables, and in-hospital mortality. The primary outcome measure was in-hospital mortality. Secondary outcome measures included hospital length of stay, intensive care unit days, and ventilator days. Results: A total of 32,746 subjects with SF were included. Motor vehicle crash (MVC) was the most common mechanism (84%) in this group and SF was present in 3.7% of all patients admitted after MVC. The mean age was 51 y, 66% were males, and most were white (74%). Overall in-hospital mortality was 8.8% and mortality with isolated SF was 3.5%. Increasing thoracic fracture burden (rib fracture, clavicular fracture, and scapular fracture) was associated with increasing hospital length of stay, intensive care unit days, ventilator days, and mortality. On multivariate regression analysis, other significant predictors of mortality were cardiac arrest, acute respiratory distress syndrome, pulmonary embolism, blunt cardiac injury, pulmonary contusion, increasing age, and lack of insurance. Conclusions: SFs occur in 3.7% of victims after MVC. With isolated SF, the mortality rate is low (3.5%); the tendency for poorer outcomes is most heavily influenced by associated injuries (pulmonary contusions, other thoracic fractures), complications (cardiac arrest, pulmonary embolism, acute respiratory distress syndrome), comorbidities (currently on or requiring dialysis, residual neurologic deficit from stroke), and lack of insurance. (C) 2014 Elsevier Inc. All rights reserved. C1 [Yeh, D. Dante; Hwabejire, John O.; DeMoya, Marc A.; Alam, Hasan B.; King, David R.; Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg,Med Sch, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St 810, Boston, MA 02114 USA. EM dyeh2@partners.org OI King, David/0000-0003-1028-1478 NR 17 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2014 VL 186 IS 1 BP 39 EP 43 DI 10.1016/j.jss.2013.08.025 PG 5 WC Surgery SC Surgery GA 274TJ UT WOS:000328628800006 PM 24135374 ER PT J AU Johnson, PJ Schmidt, DE Duvvuri, U AF Johnson, Paul J. Schmidt, David E. Duvvuri, Umamaheswar TI Output control of da Vinci surgical system's surgical graspers SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Robotic surgery; da Vinci; User interface; Usability ID ASSISTED LAPAROSCOPIC SURGERY; MINIMALLY INVASIVE SURGERY; ROBOTIC SURGERY; HAPTIC FEEDBACK; PERFORMANCE; DAMAGE; STANDARD AB Introduction: The number of robot-assisted surgeries performed with the da Vinci surgical system has increased significantly over the past decade. The articulating movements of the robotic surgical grasper are controlled by grip controls at the master console. The user interface has been implicated as one contributing factor in surgical grasping errors. The goal of our study was to characterize and evaluate the user interface of the da Vinci surgical system in controlling surgical graspers. Materials and methods: An angular manipulator with force sensors was used to increment the grip control angle as grasper output angles were measured. Input force at the grip control was simultaneously measured throughout the range of motion. Pressure film was used to assess the maximum grasping force achievable with the endoscopic grasping tool. Results: The da Vinci robot's grip control angular input has a nonproportional relationship with the grasper instrument output. The grip control mechanism presents an intrinsic resistant force to the surgeon's fingertips and provides no haptic feedback. The da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local pressure. Conclusions: The angular and force input at the grip control of the da Vinci robot's surgical graspers is nonproportional to the grasper instrument's output. Understanding the true relationship of the grip control input to grasper instrument output may help surgeons understand how to better control the surgical graspers and promote fewer grasping errors. (C) 2014 Elsevier Inc. All rights reserved. C1 [Johnson, Paul J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Schmidt, David E.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Hlth Syst, Pittsburgh, PA 15213 USA. RP Johnson, PJ (reprint author), Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Sch Med, Suite 500,203 Lothrop St, Pittsburgh, PA 15213 USA. EM pjohnsonj@gmail.com FU PNC Foundation; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX Departmental Startup Funds, and the PNC Foundation (Dr. Duvvuri, Department of Otolaryngology, University of Pittsburgh). This material is based on the work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. This work does not represent the views of the United States Government or the Department of Veterans Affairs. NR 29 TC 2 Z9 2 U1 2 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2014 VL 186 IS 1 BP 56 EP 62 DI 10.1016/j.jss.2013.07.032 PG 7 WC Surgery SC Surgery GA 274TJ UT WOS:000328628800008 PM 23968806 ER PT J AU Whelan, SP Carchman, EH Kautza, B Nassour, I Mollen, K Escobar, D Gomez, H Rosengart, MA Shiva, S Zuckerbraun, BS AF Whelan, Sean P. Carchman, Evie H. Kautza, Benjamin Nassour, Ibrahim Mollen, Kevin Escobar, Daniel Gomez, Hernando Rosengart, Matthew A. Shiva, Sruti Zuckerbraun, Brian S. TI Polymicrobial sepsis is associated with decreased hepatic oxidative phosphorylation and an altered metabolic profile SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Metabolomic; Carbohydrate; Amino Acid; fatty acid; Lipopolysaccharide ID ORGAN FAILURE; MITOCHONDRIAL DYSFUNCTION; ENERGY SENSOR; INJURY; MECHANISM; HYPOXIA AB Background: Organ failure in sepsis accounts for significant mortality worldwide. Mitochondrial and metabolic responses are central to the overall response of the cell, and thus of the organ and organism. Adaptive responses in metabolism are critical to the recovery at the cellular level. The purpose of these investigations was to test the hypothesis that sepsis is associated with decreased aerobic respiration and significant metabolic changes in the liver. Methods: C57BL/6 mice underwent cecal ligation and puncture (CLP) with a 21 gauge needle or an operation without CLP. Mice were euthanized from 0e24 h after the procedure and liver tissue was harvested. Tissue oxygen consumption and mitochondrial complex activity were measured. Global biochemical profiles of 311 metabolites were performed at the 8-h time point (n = 8/group) and analyzed by gas chromatographye-mass spectrometry and liquid chromatography tandem mass spectrometry platforms by Metabolon (Durham, North Carolina). The influence of lipopolysaccharide (LPS) on aerobic and anaerobic respiration in primary mouse hepatocytes was also investigated. Results: CLP in vivo or LPS in vitro resulted in a significant decrease in hepatic oxygen consumption. There was a significant decrease in oxidative phosphorylation measured at 12 h. LPS also resulted in a significant increase in anaerobic respiration in hepatocytes. Interestingly, the metabolomic analysis resulted in a metabolic shift in the liver from carbohydrate-based energy to utilization of fatty acids and amino acids. This included an increase in every tricarboxylic acid cycle intermediate and derivative, suggesting an increased flux into the cycle from fatty acid beta-oxidation and anaplerotic contributions from amino acids. Conclusions: Sepsis results in a metabolic response and profile consistent with increased anaerobic respiration, which occurs prior to significant changes in hemodynamics. The metabolic responses of cells and organs may be important adaptive responses to prevent organ failure and death. (C) 2014 Published by Elsevier Inc. C1 [Whelan, Sean P.; Carchman, Evie H.; Kautza, Benjamin; Nassour, Ibrahim; Mollen, Kevin; Escobar, Daniel; Rosengart, Matthew A.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Gomez, Hernando; Rosengart, Matthew A.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Surg Serv Line, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, F1271 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu OI Nassour, Ibrahim/0000-0002-9845-1074 FU NHLBI NIH HHS [T32 HL098036]; NIGMS NIH HHS [R01 GM082830] NR 25 TC 7 Z9 8 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2014 VL 186 IS 1 BP 297 EP 303 DI 10.1016/j.jss.2013.08.007 PG 7 WC Surgery SC Surgery GA 274TJ UT WOS:000328628800053 PM 24054495 ER PT J AU Hwabejire, JO Lu, J Liu, BL Li, YQ Halaweish, I Alam, HB AF Hwabejire, John O. Lu, Jennifer Liu, Baoling Li, Yongqing Halaweish, Ihab Alam, Hasan B. TI Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Hemorrhagic shock; Valproic acid; Histone deacetylase inhibitors; Dose optimization ID GLYCOGEN-SYNTHASE KINASE-3; TRAUMATIC BRAIN-INJURY; ACUTE LUNG INJURY; NF-KAPPA-B; PHARMACOLOGICAL RESUSCITATION; HISTONE DEACETYLASE; ISCHEMIA-REPERFUSION; RODENT MODEL; BETA-CATENIN; PATHWAY AB Background: Valproic acid (VPA) has been shown to improve survival in animal models of hemorrhagic shock at a dose of 300 mg/kg. Our aim was to identify the ideal dose through dose-escalation, split-dosing, and dose de-escalation regimens. Materials and methods: Rats were subjected to sublethal 40% hemorrhage and treated with vehicle or VPA (dose of 300, 400, or 450 mg/kg) after 30 min of shock. Acetylated histones and activated proteins from the PI3K Akt GSK-3 beta survival pathway at different time points were quantified by Western blot analysis. In a similar model, a VPA dose of 200 mg/kg followed 2 h later by another dose of 100 mg/kg was administered. Finally, animals were subjected to a lethal 50% hemorrhage and VPA was administered in a dose de-escalation manner (starting at dose of 300 mg/kg) until a significant drop in percent survival was observed. Results: Larger doses of VPA resulted in greater acetylation of histone 3 and increased activation of PI3K pathway proteins. Dose-dependent differences were significant in histone acetylation but not in the activation of the survival pathway proteins. Split-dose administration of VPA resulted in similar results to a single full dose. Survival was as follows: 87.5% with 300 and 250 mg/kg of VPA, 50% with 200 mg/kg of VPA, and 14% with vehicle-treated animals. Conclusions: Although higher doses of VPA result in greater histone acetylation and activation of prosurvival protein signaling, doses as low as 250 mg/kg of VPA confer the same survival advantage in lethal hemorrhagic shock. Also, VPA can be given in a split-dose fashion without a reduction in its cytoprotective effectiveness. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hwabejire, John O.; Lu, Jennifer; Liu, Baoling; Li, Yongqing; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA USA. [Liu, Baoling; Halaweish, Ihab; Alam, Hasan B.] Univ Michigan, Dept Surg, Gen Surg Sect, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Dept Surg, Gen Surg Sect, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu FU Office of Naval Research [N000140910378]; NIH [R01 GM084127] FX Funded by a grant from the Office of Naval Research (N000140910378; PI: H.B.A.) and NIH (R01 GM084127; PI: H.B.A.). NR 46 TC 11 Z9 11 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2014 VL 186 IS 1 BP 363 EP 370 DI 10.1016/j.jss.2013.09.016 PG 8 WC Surgery SC Surgery GA 274TJ UT WOS:000328628800061 PM 24135375 ER PT J AU Dagher, J Reese, T Bilgin, A AF Dagher, Joseph Reese, Timothy Bilgin, Ali TI High-Resolution, Large Dynamic Range Field Map Estimation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MR phase; field map estimation; field inhomogeneity; phase unwrapping ID GEOMETRIC DISTORTION; IMAGES; MRI AB Purpose We present a theory and a corresponding method to compute high-resolution field maps over a large dynamic range. Theory and MethodsWe derive a closed-form expression for the error in the field map value when computed from two echoes. We formulate an optimization problem to choose three echo times which result in a pair of maximally distinct error distributions. We use standard field mapping sequences at the prescribed echo times. We then design a corresponding estimation algorithm which takes advantage of the optimized echo times to disambiguate the field offset value. ResultsWe validate our method using high-resolution images of a phantom at 7T. The resulting field maps demonstrate robust mapping over both a large dynamic range, and in low SNR regions. We also present high-resolution offset maps in vivo using both, GRE and multiecho gradient echo sequences. Even though the proposed echo time spacings are larger than the well known phase aliasing cutoff, the resulting field maps exhibit a large dynamic range without the use of phase unwrapping or spatial regularization techniques. ConclusionWe demonstrate a novel three-echo field map estimation method which overcomes the traditional noise-dynamic range trade-off. Magn Reson Med 71:105-117, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Dagher, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Dagher, Joseph; Bilgin, Ali] Univ Arizona, Dept Elect & Comp Engn, Tucson, AZ 85721 USA. [Reese, Timothy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imag, Boston, MA USA. [Bilgin, Ali] Univ Arizona, Dept Biomed Engn, Tucson, AZ USA. [Bilgin, Ali] Univ Arizona, BIO5 Inst, Tucson, AZ USA. RP Dagher, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM jdagher@email.arizona.edu FU NIH [T32EB013180] FX Grant sponsor: NIH; Grant number: T32EB013180. NR 27 TC 6 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2014 VL 71 IS 1 BP 105 EP 117 DI 10.1002/mrm.24636 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 274BO UT WOS:000328580300013 PM 23401245 ER PT J AU Iezzoni, LI Yu, J Wint, AJ Smeltzer, SC Ecker, JL AF Iezzoni, Lisa I. Yu, Jun Wint, Amy J. Smeltzer, Suzanne C. Ecker, Jeffery L. TI Conditions Causing Disability and Current Pregnancy Among US Women With Chronic Physical Disabilities SO MEDICAL CARE LA English DT Article DE disability; pregnancy; mobility; comorbidities; National Health Interview Survey ID SPINAL-CORD-INJURY; MULTIPLE-SCLEROSIS; REPRODUCTIVE HEALTH; MATERNAL OBESITY; CEREBRAL-PALSY; OUTCOMES; ARTHRITIS; RELAPSES; ISSUES; ADULTS AB Background:Growing numbers of reproductive-age US women with chronic physical disabilities (CPD) are becoming pregnant. Little is known about the health conditions causing their CPD.Objectives:To identify health conditions causing CPD among reproductive-age women and specifically among currently pregnant women.Research Design:Cross-sectional, nationally representative National Health Interview Survey data from 2006 to 2011.Subjects:A total of 6043 civilian, noninstitutionalized women aged 18-49 with CPD.Measures:National Health Interview Survey asks about various movement difficulties and their underlying causes and about current pregnancy. We used responses from 8 movement difficulty and other questions to identify women with mobility difficulties caused by chronic physical health conditions.Results:Among women with CPD, 2.0% report current pregnancy, with pregnancy rates falling monotonically as CPD severity rises. Regardless of pregnancy, 20.8% report 2 causes for their CPD, and 12.7% report 3+ causes; the most common causes are arthritis, back or neck problems, and other musculoskeletal conditions. Compared with nonpregnant women, currently pregnant women report fewer causal conditions: 15.8% report 2 causes and 8.0% 3+ causes; back or neck problems are reported most frequently, followed by musculoskeletal problems and arthritis. Multivariable logistic regression analyses predicting current pregnancy controlling for age category and individual common causes of CPD found that no cause was significantly associated with higher or lower adjusted odds of pregnancy.Conclusion:Almost one quarter of currently pregnant women with CPD report more than one cause for their disability. Further research will needed to examine how obstetrical needs vary for depending on the cause of a pregnant woman's disability. C1 [Iezzoni, Lisa I.; Yu, Jun; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Smeltzer, Suzanne C.] Villanova Univ, Coll Nursing, Ctr Nursing Res, Villanova, PA 19085 USA. [Ecker, Jeffery L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Ecker, Jeffery L.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org FU NIH [2010A05384] FX Funded by the NIH, Grant Number: 2010A05384. NR 41 TC 6 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2014 VL 52 IS 1 BP 20 EP 25 DI 10.1097/MLR.0000000000000015 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 275UG UT WOS:000328702600005 PM 24220686 ER PT J AU Shahian, DM Liu, X Meyer, GS Torchiana, DF Normand, SLT AF Shahian, David M. Liu, Xiu Meyer, Gregg S. Torchiana, David F. Normand, Sharon-Lise T. TI Hospital Teaching Intensity and Mortality for Acute Myocardial Infarction, Heart Failure, and Pneumonia SO MEDICAL CARE LA English DT Article DE academic medical center; clinical outcomes; health care reform ID QUALITY-OF-CARE; ACADEMIC-MEDICAL-CENTER; HEALTH-CARE; INTERHOSPITAL TRANSFERS; NONTEACHING HOSPITALS; ADJUSTED MORTALITY; SURGICAL OUTCOMES; PATIENT OUTCOMES; REFERRAL CENTER; CRITICALLY-ILL AB Background:Under the Affordable Care Act, health care reimbursement will increasingly be linked to quality and costs. In this environment, teaching hospitals will be closely scrutinized, as their care is often more expensive. Furthermore, although they serve vital roles in education, research, management of complex diseases, and care of vulnerable populations, debate continues as to whether teaching hospitals deliver better outcomes for common conditions.Objective:To determine the association between risk-standardized mortality and teaching intensity for 3 common conditions.Research Design:Using CMS models, 30-day risk-standardized mortality rates were compared among US hospitals classified as Council of Teaching Hospital (COTH) members, non-COTH teaching hospitals, or nonteaching hospitals. These analyses were repeated using ratios of interns and residents to beds to classify teaching intensity.Subjects:The study cohort included Medicare fee-for-service beneficiaries aged 66 years or older hospitalized in acute care hospitals during 2009-2010 for acute myocardial infarction (N=342,145), heart failure (N=647,081), or pneumonia (N=598,366).Outcome Measure:The 30-day risk-standardized mortality rates for each condition, stratified by teaching intensity.Results:For each diagnosis, compared with nonteaching hospitals there was a 10% relative reduction in the adjusted odds of mortality for patients admitted to COTH hospitals and a 6%-7% relative reduction for patients admitted to non-COTH teaching hospitals. These findings were insensitive to the method of classifying teaching intensity and only partially explained by higher teaching hospital volumes.Conclusions:Health care reimbursement strategies designed to increase value should consider not only the costs but also the superior clinical outcomes at teaching hospitals for certain common conditions. C1 [Shahian, David M.; Liu, Xiu; Torchiana, David F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meyer, Gregg S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 49 TC 8 Z9 10 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2014 VL 52 IS 1 BP 38 EP 46 DI 10.1097/MLR.0000000000000005 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 275UG UT WOS:000328702600008 PM 24322988 ER PT J AU Aronis, KN Mantzoros, CS AF Aronis, Konstantinos N. Mantzoros, Christos S. TI Novel concepts in lipoprotein particle metabolism and regulation SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; LDL CHOLESTEROL; SIZE; APOLIPOPROTEIN; EXERCISE; HDL; LEVEL C1 [Aronis, Konstantinos N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. Boston Univ, Boston Med Ctr, Dept Med, Boston, MA 02217 USA. RP Aronis, KN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. EM Konstantinos.aronis@bmc.org; Dr.karonis@hotmail.com RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 NR 38 TC 2 Z9 2 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2014 VL 63 IS 1 BP 1 EP 4 DI 10.1016/j.metabol.2013.08.002 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 277DP UT WOS:000328799400001 PM 24054823 ER PT J AU Thaipisuttikul, I Hittle, LE Chandra, R Zangari, D Dixon, CL Garrett, TA Rasko, DA Dasgupta, N Moskowitz, SM Malmstrom, L Goodlett, DR Miller, SI Bishop, RE Ernst, RK AF Thaipisuttikul, Iyarit Hittle, Lauren E. Chandra, Ramesh Zangari, Daniel Dixon, Charneal L. Garrett, Teresa A. Rasko, David A. Dasgupta, Nandini Moskowitz, Samuel M. Malmstroem, Lars Goodlett, David R. Miller, Samuel I. Bishop, Russell E. Ernst, Robert K. TI A divergent Pseudomonas aeruginosa palmitoyltransferase essential for cystic fibrosis-specific lipid A SO MOLECULAR MICROBIOLOGY LA English DT Article ID CATIONIC ANTIMICROBIAL PEPTIDES; GRAM-NEGATIVE BACTERIA; HYDROCARBON RULER; SALMONELLA-TYPHIMURIUM; MASS-SPECTROMETRY; POLYMYXIN RESISTANCE; INNATE IMMUNITY; I-TASSER; LIPOPOLYSACCHARIDE; PAGP AB Strains of Pseudomonas aeruginosa (PA) isolated from the airways of cystic fibrosis patients constitutively add palmitate to lipid A, the membrane anchor of lipopolysaccharide. The PhoPQ regulated enzyme PagP is responsible for the transfer of palmitate from outer membrane phospholipids to lipid A. This enzyme had previously been identified in many pathogenic Gram-negative bacteria, but in PA had remained elusive, despite abundant evidence that its lipid A contains palmitate. Using a combined genetic and biochemical approach, we identified PA1343 as the PA gene encoding PagP. Although PA1343 lacks obvious primary structural similarity with known PagP enzymes, the -barrel tertiary structure with an interior hydrocarbon ruler appears to be conserved. PA PagP transfers palmitate to the 3 position of lipid A, in contrast to the 2 position seen with the enterobacterial PagP. Palmitoylated PA lipid A alters host innate immune responses, including increased resistance to some antimicrobial peptides and an elevated pro-inflammatory response, consistent with the synthesis of a hexa-acylated structure preferentially recognized by the TLR4/MD2 complex. Palmitoylation commonly confers resistance to cationic antimicrobial peptides, however, increased cytokine production resulting in inflammation is not seen with other palmitoylated lipid A, indicating a unique role for this modification in PA pathogenesis. C1 [Thaipisuttikul, Iyarit; Hittle, Lauren E.; Chandra, Ramesh; Rasko, David A.; Ernst, Robert K.] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA. [Thaipisuttikul, Iyarit] Mahidol Univ, Fac Med, Dept Microbiol, Siriraj Hosp, Bangkok 10700, Thailand. [Zangari, Daniel; Dixon, Charneal L.; Bishop, Russell E.] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8S 4K1, Canada. [Zangari, Daniel; Dixon, Charneal L.; Bishop, Russell E.] McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4K1, Canada. [Garrett, Teresa A.] Vassar Coll, Dept Chem, Poughkeepsie, NY 12604 USA. [Dasgupta, Nandini; Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Malmstroem, Lars] Swiss Fed Inst Technol, Inst Mol Syst Biol, Zurich, Switzerland. [Goodlett, David R.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Miller, Samuel I.] Univ Washington, Dept Microbiol, Seattle, WA 98115 USA. [Miller, Samuel I.] Univ Washington, Dept Immunol, Seattle, WA 98115 USA. [Miller, Samuel I.] Univ Washington, Dept Genome Sci, Seattle, WA 98115 USA. RP Ernst, RK (reprint author), Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA. EM bishopr@mcmaster.ca; rkernst@umaryland.edu RI Chandra, Ramesh/K-7672-2012; Ernst, Richard/I-1870-2016; OI Chandra, Ramesh/0000-0002-4473-5071; David, Rasko/0000-0002-7337-7154; Malmstrom, Lars/0000-0001-9885-9312 FU Canadian Institutes of Health Research [MOP-125979]; National Science Foundation [1029659]; National Institutes of Health [R01AI067653, RO1AI030479, R01AI047938] FX This study was supported by the Canadian Institutes of Health Research operating grant MOP-125979 (REB), the National Science Foundation-Major Research Instrumentation Award 1029659 (TAG) and the National Institutes of Health grants R01AI067653 (SMM), RO1AI030479 (SIM), and R01AI047938 (RKE). NR 62 TC 10 Z9 10 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2014 VL 91 IS 1 BP 158 EP 174 DI 10.1111/mmi.12451 PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 278NB UT WOS:000328895900013 PM 24283944 ER PT J AU Goldfine, AB Patti, ME AF Goldfine, Allison B. Patti, Mary Elizabeth TI Bariatric surgery for T2DM-cure, or remission and relapse? SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID TYPE-2 DIABETES-MELLITUS; GASTRIC BYPASS C1 [Goldfine, Allison B.; Patti, Mary Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [R56-DK095451, R56 DK095451, P30 DK036836, P30-DK03836] NR 10 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD JAN PY 2014 VL 10 IS 1 BP 8 EP 9 DI 10.1038/nrendo.2013.222 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275RJ UT WOS:000328694800003 PM 24165996 ER PT J AU Jochems, J Boulden, J Lee, BG Blendy, JA Jarpe, M Mazitschek, R Van Duzer, JH Jones, S Berton, O AF Jochems, Jeanine Boulden, Janette Lee, Bridgin G. Blendy, Julie A. Jarpe, Matthew Mazitschek, Ralph Van Duzer, John H. Jones, Simon Berton, Olivier TI Antidepressant-Like Properties of Novel HDAC6-Selective Inhibitors with Improved Brain Bioavailability SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE HDAC inhibitor; HDAC6; antidepressant; depression; tubulin acetylation; epigenetic ID HISTONE DEACETYLASE 6; SOCIAL DEFEAT STRESS; GLUCOCORTICOID-RECEPTOR; HDAC6 INHIBITOR; MOUSE MODEL; MICE; ACETYLATION; TUBULIN; DISEASE; ANXIETY AB HDAC inhibitors have been reported to produce antidepressant and pro-cognitive effects in animal models, however, poor brain bioavailability or lack of isoform selectivity of current probes has limited our understanding of their mode of action. We report the characterization of novel pyrimidine hydroxyl amide small molecule inhibitors of HDAC6, brain bioavailable upon systemic administration. We show that two compounds in this family, ACY-738 and ACY-775, inhibit HDAC6 with low nanomolar potency and a selectivity of 60to 1500-fold over class I HDACs. In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity, but more limited brain bioavailability, ACY-738 and ACY-775 induce dramatic increases in a-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments. Interestingly, despite a lack of detectable effect on histone acetylation, we show that ACY-738 and ACY-775 share the antidepressant-like properties of other HDAC inhibitors, such as SAHA and MS-275, in the tail suspension test and social defeat paradigm. These effects of ACY-738 and ACY-775 are directly attributable to the inhibition of HDAC6 expressed centrally, as they are fully abrogated in mice with a neural-specific loss of function of HDAC6. Furthermore, administered in combination, a behaviorally inactive dose of ACY-738 markedly potentiates the anti-immobility activity of a subactive dose of the selective serotonin reuptake inhibitor citalopram. Our results validate new isoform-selective probes for in vivo pharmacological studies of HDAC6 in the CNS and reinforce the viability of this HDAC isoform as a potential target for antidepressant development. C1 [Jochems, Jeanine; Boulden, Janette; Berton, Olivier] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lee, Bridgin G.; Blendy, Julie A.] Univ Penn, Dept Pharmacol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jarpe, Matthew; Van Duzer, John H.; Jones, Simon] Acetylon Pharmaceuticals, Boston, MA USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Berton, O (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, 125S 31st St,TRL2218, Philadelphia, PA 19104 USA. EM bertonol@mail.med.upenn.edu FU Acetylon Pharmaceuticals FX OB is inventor on patent application #61713014 'Pyrimidine hydroxyamide compounds as protein deacetylase inhibitors and methods of use thereof '. OB has received financial research support from Acetylon Pharmaceuticals. JHVD and MJ are employees of Acetylon Pharmaceuticals. RM is cofounder and member of the scientific advisory board of Acetylon Pharmaceuticals. RM has financial interests in SHAPE Pharmaceuticals and Acetylon Pharmaceuticals. He is also the inventor on IP licensed to these two entities. RM's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. JHVD and MJ and SJ are shareholders in Acetylon Pharmaceuticals. The remaining authors declare no conflict of interest. NR 55 TC 26 Z9 27 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2014 VL 39 IS 2 BP 389 EP 400 DI 10.1038/npp.2013.207 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 274DM UT WOS:000328585400016 PM 23954848 ER PT J AU Reddy, LF Lee, J Davis, MC Altshuler, L Glahn, DC Miklowitz, DJ Green, MF AF Reddy, L. Felice Lee, Junghee Davis, Michael C. Altshuler, Lori Glahn, David C. Miklowitz, David J. Green, Michael F. TI Impulsivity and Risk Taking in Bipolar Disorder and Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; psychopharmacology; behavioral sciences; dopamine ID DECISION-MAKING; TRAIT IMPULSIVITY; RATING-SCALE; TASK BART; DOPAMINERGIC MODULATION; RESPONSE-INHIBITION; REWARD; BEHAVIOR; SENSITIVITY; DEPRESSION AB Impulsive risk taking contributes to deleterious outcomes among clinical populations. Indeed, pathological impulsivity and risk taking are common in patients with serious mental illness, and have severe clinical repercussions including novelty seeking, response disinhibition, aggression, and substance abuse. Thus, the current study seeks to examine self-reported impulsivity (Barratt Impulsivity Scale) and performance-based behavioral risk taking (Balloon Analogue Risk Task) in bipolar disorder and schizophrenia. Participants included 68 individuals with bipolar disorder, 38 with schizophrenia, and 36 healthy controls. Self-reported impulsivity was elevated in the bipolar group compared with schizophrenia patients and healthy controls, who did not differ from each other. On the risk-taking task, schizophrenia patients were significantly more risk averse than the bipolar patients and controls. Aside from the diagnostic group differences, there was a significant effect of antipsychotic (AP) medication within the bipolar group: bipolar patients taking AP medications were more risk averse than those not taking AP medications. This difference in risk taking because of AP medications was not explained by history of psychosis. Similarly, the differences in risk taking between schizophrenia and bipolar disorder were not fully explained by AP effects. Implications for clinical practice and future research are discussed. C1 [Reddy, L. Felice; Lee, Junghee; Davis, Michael C.; Altshuler, Lori; Green, Michael F.] MIRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Lee, Junghee; Davis, Michael C.; Altshuler, Lori; Miklowitz, David J.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Glahn, David C.] Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Glahn, David C.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Reddy, LF (reprint author), MIRECC, VA Greater Los Angeles Healthcare Syst, Bldg 210,11301 Wilshire Blvd Room 117, Los Angeles, CA 90073 USA. EM lena.reddy@va.gov RI Lee, Junghee/C-5226-2014; Davis, Michael/L-8920-2013; OI Lee, Junghee/0000-0001-9567-8700; Davis, Michael/0000-0003-2293-5694; Miklowitz, David/0000-0002-9647-6147 FU Amgen; Sepracor; Eli Lilly; Takeda Pharmaceuticals North America; H. Lundbeck A/S; Sunovion Pharmaceuticals Inc.; National Institute of Mental Health (NIMH); National Association for Research on Schizophrenia and Depression (NARSAD); Danny Alberts Foundation; Attias Family Foundation; Robert L Sutherland Foundation FX Dr Green has served as a consultant for Abbott Laboratories, Amgen, Biogen, Mnemosyne, Roche, and Shire. He has received research support from Amgen. Dr Altshuler has received past funding from Sepracor (advisory board honoraria, January 2010), Eli Lilly (consultant, September 2010), and Takeda Pharmaceuticals North America, and H. Lundbeck A/S (advisory board honoraria, October 2012); and past and potential future funding from Sunovion Pharmaceuticals Inc. (advisory board honoraria, Jan 2013). Dr Miklowitz has received research funding from the National Institute of Mental Health (NIMH), the National Association for Research on Schizophrenia and Depression (NARSAD), the Danny Alberts Foundation, the Attias Family Foundation, and the Robert L Sutherland Foundation; and book royalties from Guilford Press and John Wiley & Sons. Dr Davis is named as a co-inventor on a University of California provisional patent application entitled 'Methods of using (S)-Hydroxyzine and (R)-Hydroxyzine.' Dr Reddy, Dr Glahn, and Dr Lee have no conflicts of interests or disclosures. NR 50 TC 21 Z9 22 U1 4 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2014 VL 39 IS 2 BP 456 EP 463 DI 10.1038/npp.2013.218 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 274DM UT WOS:000328585400022 PM 23963117 ER PT J AU Decelle, EA Cheng, LL AF Decelle, Emily A. Cheng, Leo L. TI High-resolution magic angle spinning H-1 MRS in prostate cancer SO NMR IN BIOMEDICINE LA English DT Review DE prostate cancer; high-resolution magic angle spinning (HRMAS); MRS; intact tissue ID MAGNETIC-RESONANCE-SPECTROSCOPY; HR-MAS SPECTROSCOPY; PROTON NMR; TISSUE SAMPLES; MESSENGER-RNA; METABOLITES; SPERMINE; H-1-NMR; BENIGN; GROWTH AB Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide, largely as a result of the increased use of the annual serum prostate-specific antigen (PSA) screening test for detection. PSA screening has saved lives, but it has also resulted in the overtreatment of many patients with PCa because of a limited ability to accurately localize and characterize PCa lesions through imaging. High-resolution magic angle spinning (HRMAS) H-1 MRS has proven to be a strong potential clinical tool for PCa diagnosis and prognosis. The HRMAS technique allows valuable metabolic information to be obtained from ex vivo intact tissue samples and also enables the performance of histopathology on the same tissue specimens. Studies have found that the quantification of individual metabolite levels and metabolite ratios, as well as metabolomic profiles, shows strong potential to improve accuracy in PCa detection, diagnosis and monitoring. Ex vivo HRMAS is also a valuable tool for the interpretation of in vivo results, including the localization of tumors, and thus has the potential to improve in vivo diagnostic tests used in the clinic. Here, we primarily review publications of HRMAS H-1 MRS and its use for the study of intact human prostate tissue. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Decelle, Emily A.; Cheng, Leo L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Decelle, Emily A.; Cheng, Leo L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Cheng, LL (reprint author), 149 13th St,CNY 6, Charlestown, MA 02139 USA. EM cheng@nmr.mgh.harvard.edu FU Public Health Service/National Institutes of Health (PHS/NIH) [CA115746, CA115746S2, CA162959, CA141139]; Massachusetts General Hospital (MGH) A. A. Martinos Center for Biomedical Imaging FX This work was supported by Public Health Service/National Institutes of Health (PHS/NIH) grants CA115746, CA115746S2, CA162959 and CA141139 (LLC), and the Massachusetts General Hospital (MGH) A. A. Martinos Center for Biomedical Imaging. NR 49 TC 7 Z9 8 U1 0 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD JAN PY 2014 VL 27 IS 1 BP 90 EP 99 DI 10.1002/nbm.2944 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 274JU UT WOS:000328603400009 PM 23529951 ER PT J AU Duarte, VM Liu, YF Rafizadeh, S Tajima, T Nabili, V Wang, MB AF Duarte, Victor M. Liu, Yuan F. Rafizadeh, Sassan Tajima, Tracey Nabili, Vishad Wang, Marilene B. TI Comparison of Dental Health of Patients with Head and Neck Cancer Receiving IMRT vs Conventional Radiation SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE dental health; radiation and dental health; IMRT and dental ID INTENSITY-MODULATED RADIOTHERAPY; THERAPY; XEROSTOMIA; DISEASE AB Objective To analyze the dental health of patients with head and neck cancer who received comprehensive dental care after intensity-modulated radiation therapy (IMRT) compared with radiation therapy (RT). Study Design Historical cohort study. Setting Veteran Affairs (VA) hospital. Subjects and Methods In total, 158 patients at a single VA hospital who were treated with RT or IMRT between 2003 and 2011 were identified. A complete dental evaluation was performed prior to radiation treatment, including periodontal probing, tooth profile, cavity check, and mobility. The dental treatment plan was formulated to eliminate current and potential dental disease. The rates of dental extractions, infections, caries, mucositis, xerostomia, and osteoradionecrosis (ORN) were analyzed, and a comparison was made between patients treated with IMRT and those treated with RT. Results Of the 158 patients, 99 were treated with RT and 59 were treated with IMRT. Compared with those treated with IMRT, significantly more patients treated with RT exhibited xerostomia (46.5% vs 16.9%; P < .001; odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.52), mucositis (46.5% vs 16.9%; P < .001; OR, 0.24; 95% CI, 0.11-0.52), and ORN (10.1% vs 0%; P = .014; OR, 0.07; 95% CI, 0.00-1.21). However, significantly more patients treated with IMRT were edentulous by the conclusion of radiation treatment (32.2% vs 11.1%; P = .002; OR, 3.8; 95% CI, 1.65-8.73). Conclusion Patients who were treated with IMRT had fewer instances of dental disease, more salivary flow, and fewer requisite posttreatment extractions compared with those treated with RT. The number of posttreatment extractions has been reduced with the advent of IMRT and more so with a complete dental evaluation prior to treatment. C1 [Duarte, Victor M.; Liu, Yuan F.; Rafizadeh, Sassan; Nabili, Vishad; Wang, Marilene B.] Univ Calif Los Angeles, David E Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Duarte, Victor M.; Tajima, Tracey; Nabili, Vishad; Wang, Marilene B.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tajima, Tracey] Univ Calif Los Angeles, Sch Dent, Dept Oral Med, Los Angeles, CA 90095 USA. RP Duarte, VM (reprint author), Univ Calif Los Angeles, David E Geffen Sch Med, Dept Head & Neck Surg, Ctr Hlth Sci 62 132, Los Angeles, CA 90095 USA. EM vduarte@mednet.ucla.edu OI Liu, Yuan/0000-0002-8637-661X NR 12 TC 17 Z9 18 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2014 VL 150 IS 1 BP 81 EP 86 DI 10.1177/0194599813509586 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 275QB UT WOS:000328690800013 PM 24145147 ER PT J AU Borja, MJ Schaefer, PW Boulter, DJ AF Borja, Maria J. Schaefer, Pamela W. Boulter, Daniel J. TI Case of the Season: Dural Arteriovenous Fistula Mimicking a Bithalamic Neoplasm or Viral Encephalitis SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID VENOUS DRAINAGE; DEMENTIA C1 [Borja, Maria J.; Schaefer, Pamela W.; Boulter, Daniel J.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02144 USA. RP Schaefer, PW (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02144 USA. EM pschaefer@partners.org NR 14 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JAN PY 2014 VL 49 IS 1 BP 4 EP 9 DI 10.1053/j.ro.2013.11.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 277DW UT WOS:000328800100003 PM 24342671 ER PT J AU Boulter, DJ Schaefer, PW AF Boulter, Daniel J. Schaefer, Pamela W. TI Stroke and Stroke Mimics: A Pattern-Based Approach SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID TRANSIENT GLOBAL AMNESIA; CENTRAL-NERVOUS-SYSTEM; CEREBRAL FAT-EMBOLISM; REVERSIBLE ENCEPHALOPATHY SYNDROME; DIFFUSION-WEIGHTED MRI; ACUTE ISCHEMIC-STROKE; IMAGING FINDINGS; CT ANGIOGRAPHY; INTRAARTERIAL THROMBOLYSIS; INTRAVENOUS THROMBOLYSIS C1 [Boulter, Daniel J.; Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02144 USA. RP Schaefer, PW (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02144 USA. EM pschaefer@partners.org NR 75 TC 2 Z9 2 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JAN PY 2014 VL 49 IS 1 BP 22 EP 38 DI 10.1053/j.ro.2013.10.005 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 277DW UT WOS:000328800100005 PM 24342673 ER PT J AU Ciura, VA Romero, JM AF Ciura, Viesha A. Romero, Javier M. TI Nontraumatic Acute Intraparenchymal Hemorrhage: Algorithm for Workup and Differential Diagnosis SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; REVERSIBLE ENCEPHALOPATHY SYNDROME; CEREBRAL AMYLOID ANGIOPATHY; APOLIPOPROTEIN-E GENOTYPE; MR-IMAGING FINDINGS; CT ANGIOGRAPHY; INTRACRANIAL HEMORRHAGE; ACUTE STROKE; SUBARACHNOID HEMORRHAGE C1 [Ciura, Viesha A.; Romero, Javier M.] Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. RP Romero, JM (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, 55 Fruit St,Gray 2,Rm 273 A, Boston, MA 02114 USA. EM jmromero@partners.org NR 76 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X EI 1558-4658 J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JAN PY 2014 VL 49 IS 1 BP 112 EP 126 DI 10.1053/j.ro.2013.10.002 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 277DW UT WOS:000328800100012 PM 24342680 ER PT J AU Wood, KB Li, WS Lebl, DS Ploumis, A AF Wood, Kirkham B. Li, Weishi Lebl, Darren S. Ploumis, Avraam TI Management of thoracolumbar spine fractures SO SPINE JOURNAL LA English DT Review DE Thoracolumbar; Spine; Fracture; Fracture-dislocation; Fusion; Kyphoplasty; Surgery; Outcomes ID VERTEBRAL COMPRESSION FRACTURES; POSTERIOR LIGAMENTOUS COMPLEX; BACK MUSCLE INJURY; OSTEOPOROTIC BURST FRACTURES; HIGH-DOSE METHYLPREDNISOLONE; LOAD SHARING CLASSIFICATION; TERM-FOLLOW-UP; CORD-INJURY; LUMBAR SPINE; PERCUTANEOUS VERTEBROPLASTY AB BACKGROUND CONTEXT: Traumatic fractures of the spine are most common at the thoracolumbar junction and can be a source of great disability. PURPOSE: To review the most current information regarding the pathophysiology, injury pattern, treatment options, and outcomes. STUDY DESIGN: Literature review. METHODS: Relevant articles, textbook chapters, and abstracts covering thoracolumbar spine fractures with and without neurologic deficit from 1960 to the present were reviewed. RESULTS: The thoracolumbar spine represents a unique system from a skeletal as well as neurological standpoint. The rigid rib-bearing thoracic spine articulates with the more mobile lumbar spine at the thoracolumbar junction (T10-L2), the site of most fractures. A complete examination includes a careful neurologic examination of both motor and sensory systems. CT scans best describe bony detail while MRI is most efficient at describing soft tissues and neurological structures. The most recent classification system is that of the new Thoracolumbar Injury Classification and Severity Score. The different fracture types include compression fractures, burst fractures - both stable and unstable -, flexion-distraction injuries and fracture dislocations. Their treatment, both operative and non-operative depends on the degree of bony compromise, neurological involvement, and the integrity of the posterior ligamentous complex. Minimally invasive approaches to the care of thoracolumbar injuries have become more popular, thus, the evidence regarding their efficacy is presented. Finally, the treatment of osteoporotic fractures of the thoracolumbar spine is reviewed, including vertebroplasty and kyphoplasty, their risks and controversies, and senile burst fractures, as well. CONCLUSIONS: Thoracolumbar spine fractures remain a significant source of potential morbidity. Advances in treatment have minimized the invasiveness of our surgery and in certain stable situations, eliminated it all together. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wood, Kirkham B.; Li, Weishi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lebl, Darren S.] Hosp Surg, New York, NY USA. [Ploumis, Avraam] Univ Ioninna, Ioannina 45110, Greece. RP Wood, KB (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Suite 3800,Yawkey Bldg, Boston, MA 02114 USA. EM kbwood@partners.org FU NASS; Scoliosis Research Society; DePuy Spine; Globus, Inc.; Synthes FX KBW: Stock Ownership: TranS1 (10,000 shares, 100% ownership); Scientific Advisory Board: United Health Care (C); Research Support: Investigator Salary: NASS (D); Research Support: Staff and/or Materials: Medtronic (D); Grant: Scoliosis Research Society (D); Fellowship Support: DePuy Spine (E), Globus, Inc. (E), Synthes (E). WL: Nothing to disclose. DSL: Nothing to disclose. AP: Nothing to disclose. NR 151 TC 42 Z9 55 U1 3 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD JAN PY 2014 VL 14 IS 1 BP 145 EP 164 DI 10.1016/j.spinee.2012.10.041 PG 20 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 272XN UT WOS:000328496600022 PM 24332321 ER PT J AU Agmon-Levin, N Damoiseaux, J Kallenberg, C Sack, U Witte, T Herold, M Bossuyt, X Musset, L Cervera, R Plaza-Lopez, A Dias, C Sousa, MJ Radice, A Eriksson, C Hultgren, O Viander, M Khamashta, M Regenass, S Andrade, LEC Wiik, A Tincani, A Ronnelid, J Bloch, DB Fritzler, MJ Chan, EKL Garcia-De La Torre, I Konstantinov, KN Lahita, R Wilson, M Vainio, O Fabien, N Sinico, RA Meroni, P Shoenfeld, Y AF Agmon-Levin, Nancy Damoiseaux, Jan Kallenberg, Cees Sack, Ulrich Witte, Torsten Herold, Manfred Bossuyt, Xavier Musset, Lucille Cervera, Ricard Plaza-Lopez, Aresio Dias, Carlos Sousa, Maria Jose Radice, Antonella Eriksson, Catharina Hultgren, Olof Viander, Markku Khamashta, Munther Regenass, Stephan Coelho Andrade, Luis Eduardo Wiik, Allan Tincani, Angela Ronnelid, Johan Bloch, Donald B. Fritzler, Marvin J. Chan, Edward K. L. Garcia-De la Torre, I. Konstantinov, Konstantin N. Lahita, Robert Wilson, Merlin Vainio, Olli Fabien, Nicole Sinico, Renato Alberto Meroni, Pierluigi Shoenfeld, Yehuda TI International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review DE Autoantibodies; Autoimmunity; Systemic Lupus Erythematosus; SjOgren's Syndrome ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EXTRACTABLE NUCLEAR ANTIGENS; INDIRECT IMMUNOFLUORESCENCE; RHEUMATIC-DISEASES; HEALTHY-INDIVIDUALS; DIAGNOSTIC-ACCURACY; AUTOIMMUNE-DISEASES; COMMERCIAL KITS; ANA; GUIDELINES AB Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested. C1 [Agmon-Levin, Nancy; Shoenfeld, Yehuda] Chaim Sheba Med Ctr, Zabludowicz Ctr Autoimmune Dis, Tel Aviv, Israel. [Agmon-Levin, Nancy; Shoenfeld, Yehuda] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Damoiseaux, Jan] Maastricht Univ, Med Ctr, Cent Diagnost Lab, Maastricht, Netherlands. [Kallenberg, Cees] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands. [Sack, Ulrich] Univ Leipzig, Inst Clin Immunol & Transfus Med, D-04109 Leipzig, Germany. [Witte, Torsten] Sch Med, Dept Clin Immunol & Rheumatol, Hannover, Germany. [Herold, Manfred] Med Univ Innsbruck, Rheumatol Unit, Dept Internal Med 1, A-6020 Innsbruck, Austria. [Herold, Manfred] Univ Hosp Leuven, Louvain, Belgium. [Bossuyt, Xavier] Katholieke Univ Leuven, Dept Microbiol & Immunol, Louvain, Belgium. [Musset, Lucille] GH Pitie Salpetriere, Dept Immunol, Paris, France. [Cervera, Ricard] Hosp Clin Barcelona, Dept Autoimmune Dis, Catalonia, Spain. [Plaza-Lopez, Aresio] Hosp Univ Pueta Hierro Majadahonda, Serv Inmunol, Madrid, Spain. [Dias, Carlos] S Joao Hosp, Dept Med, Autoimmune Dis Unit, Oporto, Portugal. [Sousa, Maria Jose] Fernando Fonseca Hosp, Autoimmun & PreNatal Diagnost Lab Unit, Oporto, Portugal. [Radice, Antonella] Azienda Osped Osped San Carlo Borromeo, Inst Microbiol, Milan, Italy. [Eriksson, Catharina] Umea Univ, Dept Clin Microbiol, Umea, Sweden. [Hultgren, Olof] Univ Hosp Orebro, Dept Lab Med, Orebro, Sweden. [Hultgren, Olof] Univ Orebro, SE-70182 Orebro, Sweden. [Viander, Markku] Univ Turku, Dept Med Microbiol & Immunol, Turku, Finland. [Khamashta, Munther] Kings Coll London, Div Womens Hlth, Lupus Res Lab, London WC2R 2LS, England. [Regenass, Stephan] DIA Univ Spital, Klin Immunol, Zurich, Switzerland. [Coelho Andrade, Luis Eduardo] Univ Fed Sao Paulo, Div Rheumatol, Sao Paulo, Brazil. [Wiik, Allan] Statens Serum Inst, Dept Clin Chem & Immunol, DK-2300 Copenhagen S, Denmark. [Tincani, Angela] Spedali Civil Brescia, Rheumatol & Clin Immunol Unit, Dept Clin & Expt Sci, I-25125 Brescia, Italy. [Tincani, Angela] Univ Brescia, Brescia, Italy. [Ronnelid, Johan] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Bloch, Donald B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Harvard, MA USA. [Bloch, Donald B.] Harvard Univ, Sch Med, Harvard, MA USA. [Fritzler, Marvin J.] Univ Calgary, Fac Med, Calgary, AB, Canada. [Chan, Edward K. L.] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA. [Garcia-De la Torre, I.] Hosp Gen Occidente Seguro Social, Dept Immunol & Rheumatol, Guadalajara, Jalisco, Mexico. [Garcia-De la Torre, I.] Univ Guadalajara, Guadalajara 44430, Jalisco, Mexico. [Lahita, Robert] Newark Beth Israel Med Ctr UMDNJ, Newark, NJ USA. [Lahita, Robert] Newark Beth Israel Med Ctr UMDNJ, VP, Newark, NJ USA. [Vainio, Olli] Univ Oulu, Inst Diagnost, Dept Med Microbiol & Immunol, Oulu, Finland. [Vainio, Olli] NordLab Oulu, Oulu, Finland. [Fabien, Nicole] CH Lyon Sud, Dept Immunol, Pierre Benite, France. [Sinico, Renato Alberto] Azienda Osped Osped San Carlo Borromeo, Clin Immunol Unit, Milan, Italy. [Sinico, Renato Alberto] Azienda Osped Osped San Carlo Borromeo, Renal Unit, Milan, Italy. [Meroni, Pierluigi] Univ Milan, Div Rheumatol, Ist G Pini, Ist Auxol Italiano, Milan, Italy. [Shoenfeld, Yehuda] Tel Aviv Univ, Sackler Fac Med, Laura Schwarz Kip Chair Res Autoimmune Dis, IL-69978 Tel Aviv, Israel. RP Shoenfeld, Y (reprint author), Chaim Sheba Med Ctr, Ctr Autoimmune Dis, IL-52621 Tel Hashomer, Israel. EM shoenfel@post.tau.ac.il RI Damoiseaux, Jan/B-8993-2009; Andrade, Luis/D-1245-2012; Tincani, Angela/E-7608-2010; Witte, Torsten/B-5783-2016; Sack, Ulrich/J-6301-2015; Meroni, Pier Luigi/K-8473-2016 OI Andrade, Luis/0000-0001-8742-9931; Sack, Ulrich/0000-0002-7813-0492; Meroni, Pier Luigi/0000-0002-3394-1451 NR 48 TC 99 Z9 106 U1 5 U2 20 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2014 VL 73 IS 1 BP 17 EP 23 DI 10.1136/annrheumdis-2013-203863 PG 7 WC Rheumatology SC Rheumatology GA 263VC UT WOS:000327835100009 PM 24126457 ER PT J AU Rasmussen, A Ice, JA Li, H Grundahl, K Kelly, JA Radfar, L Stone, DU Hefner, KS Anaya, JM Rohrer, M Gopalakrishnan, R Houston, GD Lewis, DM Chodosh, J Harley, JB Hughes, P Maier-Moore, JS Montgomery, CG Rhodus, NL Farris, AD Segal, BM Jonsson, R Lessard, CJ Scofield, RH Sivils, KLM AF Rasmussen, Astrid Ice, John A. Li, He Grundahl, Kiely Kelly, Jennifer A. Radfar, Lida Stone, Donald U. Hefner, Kimberly S. Anaya, Juan-Manuel Rohrer, Michael Gopalakrishnan, Rajaram Houston, Glen D. Lewis, David M. Chodosh, James Harley, John B. Hughes, Pamela Maier-Moore, Jacen S. Montgomery, Courtney G. Rhodus, Nelson L. Farris, A. Darise Segal, Barbara M. Jonsson, Roland Lessard, Christopher J. Scofield, R. Hal Sivils, Kathy L. Moser TI Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article DE Sjogren's syndrome; Classification; Diagnosis ID PREVALENCE; COMMUNITY; REGISTRY; TESTS AB Objective To compare the performance of the American-European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjogren's Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. Methods In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. Results Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was 1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG-/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. Conclusions The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available. C1 [Rasmussen, Astrid; Ice, John A.; Li, He; Grundahl, Kiely; Kelly, Jennifer A.; Maier-Moore, Jacen S.; Montgomery, Courtney G.; Farris, A. Darise; Lessard, Christopher J.; Scofield, R. Hal; Sivils, Kathy L. Moser] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Li, He; Houston, Glen D.; Lewis, David M.; Lessard, Christopher J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Radfar, Lida] Univ Oklahoma, Coll Dent, Dept Oral Diag & Radiol, Oklahoma City, OK USA. [Stone, Donald U.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. [Hefner, Kimberly S.] Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA. [Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia. [Rohrer, Michael] Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA. [Gopalakrishnan, Rajaram] Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral Pathol, Minneapolis, MN 55455 USA. [Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Hughes, Pamela] Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA. [Rhodus, Nelson L.] Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Jonsson, Roland] Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway. [Jonsson, Roland] Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway. [Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Scofield, R. Hal] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. RP Sivils, KLM (reprint author), Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St,MS57, Oklahoma City, OK 73104 USA. EM sivilsk@omrf.org RI Anaya, Juan-Manuel/J-1960-2016; OI Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Houston, Graeme/0000-0002-9786-7975 FU Phileona Foundation; Oklahoma Medical Research Foundation; [5R01 AR50782]; [P50 AR0608040]; [5U19 AI 082714]; [5R01 DE018209]; [5R37AI024717-22S1] FX This publication was made possible by grants 5R01 AR50782 (KLS), P50 AR0608040 (KLS, CJL, RHS, and ADF), 5U19 AI 082714 (KLS, CJL), 5R01 DE018209 (KLS, JBH), 5R37AI024717-22S1 (JBH, AR). The contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH. Additional funding was obtained from the Phileona Foundation (KLS) and the Oklahoma Medical Research Foundation (CJL and KLS). DUS received funding from an unrestricted grant from Research to Prevent Blindness to the University of Oklahoma Department of Ophthalmology. NR 30 TC 47 Z9 49 U1 2 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2014 VL 73 IS 1 BP 31 EP 38 DI 10.1136/annrheumdis-2013-203845 PG 8 WC Rheumatology SC Rheumatology GA 263VC UT WOS:000327835100011 PM 23968620 ER PT J AU Wallace, DJ Kalunian, K Petri, MA Strand, V Houssiau, FA Pike, M Kilgallen, B Bongardt, S Barry, A Kelley, L Gordon, C AF Wallace, Daniel J. Kalunian, Kenneth Petri, Michelle A. Strand, Vibeke Houssiau, Frederic A. Pike, Marilyn Kilgallen, Brian Bongardt, Sabine Barry, Anna Kelley, Lexy Gordon, Caroline TI Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article DE Systemic Lupus Erythematosus; Treatment; B cells ID B-CELLS; MONOCLONAL-ANTIBODY; INDEX; CD22; TRIAL AB Objective To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). Methods A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200mg cumulative dose (cd) (100mg every other week (EOW)), 800mg cd (400mg EOW), 2400mg cd (600mg weekly), 2400mg cd (1200mg EOW), or 3600mg cd (1800mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Results Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400mg epratuzumab (OR for 600mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Conclusions Treatment with epratuzumab 2400mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing. C1 [Wallace, Daniel J.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Kalunian, Kenneth] UCSD Sch Med, La Jolla, CA USA. [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Strand, Vibeke] Stanford Univ, Div Immunol & Rheumatol, Palo Alto, CA 94304 USA. [Houssiau, Frederic A.] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. [Pike, Marilyn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kilgallen, Brian; Barry, Anna; Kelley, Lexy] UCB Pharma, Raleigh, NC USA. [Bongardt, Sabine] UCB Pharma, Monheim, Germany. [Gordon, Caroline] Univ Birmingham, Sch Immun & Infect, Coll Med & Dent Sci, Rheumatol Res Grp, Birmingham, W Midlands, England. [Gordon, Caroline] Univ Hosp Birmingham NHS Fdn Trust, Wellcome Trust Clin Res Facil, Birmingham, W Midlands, England. RP Wallace, DJ (reprint author), Cedars Sinai Med Ctr, 8737 Beverly Blvd,Suite 302, West Hollywood, CA 90048 USA. EM dwallace@ucla.edu FU UCB Pharma FX This study was funded by UCB Pharma. Epratuzumab was licensed for non-oncology indications by UCB Pharma from Immunomedics, Inc. Medical writing support was provided by Niall Harrison and Liz Haygreen of Darwin Healthcare Communications and was funded by UCB Pharma. NR 32 TC 97 Z9 104 U1 1 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2014 VL 73 IS 1 BP 183 EP 190 DI 10.1136/annrheumdis-2012-202760 PG 8 WC Rheumatology SC Rheumatology GA 263VC UT WOS:000327835100032 PM 23313811 ER PT J AU Bredella, MA Gill, CM Rosen, CJ Klibanski, A Torriani, M AF Bredella, Miriam A. Gill, Corey M. Rosen, Clifford J. Klibanski, Anne Torriani, Martin TI Positive effects of brown adipose tissue on femoral bone structure SO BONE LA English DT Article DE Brown adipose tissue (BAT); Bone; Structure; Muscle; Fat ID TRANSCRIPTIONAL CONTROL; FAT; ADIPOGENESIS; PRDM16; WOMEN AB Purpose: Recent studies suggest a link between brown adipose tissue (BAT) and bone. The purpose of our study was to investigate the effects of BAT on femoral bone structure. Materials and methods: We studied 105 patients (19 m, 86 f. mean age 45.5 +/- 16.1 years) who underwent F18-FDG positron emission tomography/computed tomography (PET/CT) for benign etiologies (n = 20) or follow-up of successfully treated malignancies (n = 85); mean time between PET/CT and last form of treatment was 14.8 +/- 18.0 months. BAT volume by PET/CT; femoral bone structure by CT (total femoral cross-sectional area (CSA), cortical CSA); and thigh muscle CSA and thigh subcutaneous fat CSA by CT was assessed. Results: There were positive correlations between BAT volume and total femoral CSA and cortical CSA, independent of age, BMI and history of malignancy (p < 0.05). BAT volume correlated positively with thigh muscle CSA and thigh fat CSA (p < 0.05). When total femoral CSA was entered as a dependent variable and BAT volume, age and BMI as independent variables in a forward stepwise regression model, BAT volume was the only predictor of total femoral CSA. When femoral cortical CSA was entered as a dependent variable and BAT volume, age and BMI as independent variables, BAT volume was the only predictor of femoral cortical CSA. Conclusion: BAT volume is a positive predictor of femoral bone structure and correlates positively with thigh muscle and subcutaneous fat, possibly mediated by muscle. These results provide further evidence of a positive effect of BAT on bone. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bredella, Miriam A.; Gill, Corey M.; Torriani, Martin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [R24 DK084970] FX This work was supported in part by National Institutes of Health Grant R24 DK084970. NR 20 TC 15 Z9 16 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD JAN PY 2014 VL 58 BP 55 EP 58 DI 10.1016/j.bone.2013.10.007 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270FJ UT WOS:000328304000008 PM 24140784 ER PT J AU Place, AE Frederick, NN Sallan, SE AF Place, Andrew E. Frederick, Natasha N. Sallan, Stephen E. TI Therapeutic approaches to haematological malignancies in adolescents and young adults SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE AYA Oncology; acute lymphoblastic leukaemia; acute myeloid leukaemia; Hodgkin lymphoma; non-Hodgkin lymphoma ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; LARGE-CELL LYMPHOMA; CHILDRENS ONCOLOGY GROUP; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; FARBER-CANCER-INSTITUTE; STAGE HODGKIN LYMPHOMA; 1ST COMPLETE REMISSION; HIGH-DOSE CYTARABINE AB Tremendous strides have been made in improving the outcomes of haematological malignancies (HM) over the last three decades, but adolescents and young adult (AYA) patients have not benefitted equally compared to younger and older patients. Excellent outcomes in Hodgkin lymphoma have allowed tailoring of highly effective regimens that limit the incidence of late effects. Early successes in paediatric acute lymphoblastic leukaemia set the stage for a series of studies in young adults utilizing a paediatric-type treatment strategy. These studies have determined that AYAs benefit from paediatric-type chemotherapy regimens. Despite the increased incidence of acute myeloid leukaemia and non-Hodgkin lymphoma in the AYA age group, optimal strategies for these patients have not been systematically pursued. There is renewed interest in improving HM outcomes in AYA patients and this will rely on the development of clinical trials that specifically target these patients. Understanding and addressing the unique psychosocial challenges of this population will be critical in supporting this endeavor. C1 [Place, Andrew E.; Frederick, Natasha N.; Sallan, Stephen E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Place, Andrew E.; Frederick, Natasha N.; Sallan, Stephen E.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Place, AE (reprint author), Dana Farber Canc Inst, DA3-136,450 Brookline Ave, Boston, MA 02215 USA. EM andrew_place@dfci.harvard.edu NR 97 TC 3 Z9 3 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2014 VL 164 IS 1 BP 3 EP 14 DI 10.1111/bjh.12556 PG 12 WC Hematology SC Hematology GA 263CD UT WOS:000327783300003 PM 24007213 ER PT J AU Wang, H Albadawi, H Siddiquee, Z Stone, JM Panchenko, MP Watkins, MT Stone, JR AF Wang, He Albadawi, Hassan Siddiquee, Zakir Stone, Jillian M. Panchenko, Mikhail P. Watkins, Michael T. Stone, James R. TI Altered vascular activation due to deficiency of the NADPH oxidase component p22(phox) SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Hydrogen peroxide; HnRNP-C; MMP12; NADPH oxidase; Protein kinase CK1 alpha; Protein kinase CK1 alpha LS; Reactive oxygen species; TIMP1; Vascular activation; Vascular injury ID PROTEIN-KINASE CK1-ALPHA-LS; NUCLEAR RIBONUCLEOPROTEIN-C; INDUCED CARDIAC-HYPERTROPHY; MESSENGER-RNA BINDING; ANGIOTENSIN-II; HYDROGEN-PEROXIDE; PHYSIOLOGICAL LEVELS; NEOINTIMAL FORMATION; NOX1-DEFICIENT MICE; INTIMAL HYPERPLASIA AB Background: Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play important roles in vascular activation. The p22(phox) subunit is necessary for the activity of NADPH oxidase complexes utilizing Nox1, Nox2, Nox3, and Nox4 catalytic subunits. Methods: We assessed p22(phox)-deficient mice and human tissue for altered vascular activation. Results: Mice deficient in p22(phox) were smaller than their wild-type littermates but showed no alteration in basal blood pressure. The wild-type littermates were relatively resistant to forming intimal hyperplasia following carotid ligation, and the intimal hyperplasia that developed was not altered by p22(phox) deficiency. However, at the site of carotid artery ligation, the p22(phox)-deficient mice showed significantly less vascular elastic fiber loss compared with their wild-type littermates. This preservation of elastic fibers was associated with a reduced matrix metallopeptidase (MMP) 12/tissue inhibitor of metalloproteinase (TIMP) 1 expression ratio. A similar decrease in the relative MMP12/TIMP1 expression ratio occurred in human coronary artery smooth muscle cells upon knockdown of the hydrogen peroxide responsive kinase CK1 alpha LS. In the ligated carotid arteries, the p22(phox)-deficient mice showed reduced expression of heterogeneous nuclear ribonucleoprotein C (hnRNP-C), suggesting reduced activity of CK1 alpha LS. In a lung biopsy from a human patient with p22(phox) deficiency, there was also reduced vascular hnRNP-C expression. Conclusions: These findings indicate that NADPH oxidase complexes modulate aspects of vascular activation including vascular elastic fiber loss, the MMP12/TIMP1 expression ratio, and the expression of hnRNP-C. Furthermore, these findings suggest that the effects of NADPH oxidase on vascular activation are mediated in part by protein kinase CK1 alpha LS. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wang, He; Siddiquee, Zakir; Stone, Jillian M.; Panchenko, Mikhail P.; Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Wang, He; Siddiquee, Zakir; Stone, Jillian M.; Panchenko, Mikhail P.; Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wang, He; Albadawi, Hassan; Siddiquee, Zakir; Stone, Jillian M.; Panchenko, Mikhail P.; Watkins, Michael T.; Stone, James R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Albadawi, Hassan; Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jrstone@partners.org FU Department of Pathology, Massachusetts General Hospital; Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX This work was funded by the Department of Pathology and the Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital. NR 37 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 EI 1879-1336 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JAN-FEB PY 2014 VL 23 IS 1 BP 35 EP 42 DI 10.1016/j.carpath.2013.08.003 PG 8 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 272UE UT WOS:000328485900007 PM 24035466 ER PT J AU Tirumani, SH Krajewski, KM Shinagare, AB Jagannathan, JP Ramaiya, NH AF Tirumani, Sree Harsha Krajewski, Katherine M. Shinagare, Atul B. Jagannathan, Jyothi P. Ramaiya, Nikhil H. TI Gallbladder complications associated with molecular targeted therapies: clinical and imaging features SO CLINICAL IMAGING LA English DT Article DE Molecular targeted therapies; Gallbladder complications; Acute cholecystitis; Ultrasound; CT ID RENAL-CELL CARCINOMA; ACUTE CHOLECYSTITIS; SUNITINIB; RADIOLOGISTS; PATIENT AB Objectives: To evaluate the clinical and imaging features of molecular target therapies (MTT)-associated gallbladder complications. Methods: The clinical presentation, imaging features, management, and outcome in six consecutive patients, who developed gallbladder complications while on monotherapy with MIT, were studied. Results: Imaging features included gallbladder distension, edema, hyperemia, pericholecystic fluid, and stranding. Two of the six patients were asymptomatic and continued the drug due to good response. Four of the six patients developed acute cholecystitis and required drug discontinuation temporarily or permanently with 2/4 patients requiring surgery. Conclusion: MIT can be associated with gallbladder complications that may need temporary or permanent discontinuation of the associated drug. (C) 2014 Elsevier Inc. All rights reserved. C1 [Tirumani, Sree Harsha; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Krajewski, Katherine M.; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org.com NR 18 TC 3 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD JAN-FEB PY 2014 VL 38 IS 1 BP 50 EP 55 DI 10.1016/j.clinimag.2013.08.012 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 270JG UT WOS:000328314100009 PM 24135148 ER PT S AU Banda, NK Takahashi, K AF Banda, Nirmal K. Takahashi, Kazue BE Gadjeva, M TI Analysis of the Complement Activation in Mice SO COMPLEMENT SYSTEM: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Complement; Mouse; ELISA; Assay; Activation; Pathway ID PATHWAY AB Complement activation is an important immune mechanism in mice like in humans. Murine complement is also activated via three pathways, the classical, lectin, and alternative. Complement proteins are serine proteases; thus activation of complement is proteolytic cleavage of complement proteins, which are both soluble and deposited forms. Therefore, complement pathway activation can be assayed by measuring deposited cleaved complement proteins on materials that are known to activate each pathway. In this chapter, we describe how we assay activation of these three pathways in murine system. C1 [Banda, Nirmal K.; Takahashi, Kazue] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Banda, NK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-724-2; 978-1-62703-723-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1100 BP 365 EP 371 DI 10.1007/978-1-62703-724-2_31 D2 10.1007/978-1-62703-724-2 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BJH08 UT WOS:000328153500032 PM 24218276 ER PT J AU Zinman, B Genuth, S Nathan, DM AF Zinman, Bernard Genuth, Saul Nathan, David M. TI The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study: 30th Anniversary Presentations SO DIABETES CARE LA English DT Editorial Material C1 [Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Dept Med, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Genuth, Saul] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zinman, B (reprint author), Univ Toronto, Mt Sinai Hosp, Dept Med, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. EM zinman@lunenfeld.ca RI Zinman, Bernard/E-7266-2013 FU NCATS NIH HHS [UL1 TR000457] NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2014 VL 37 IS 1 BP 8 EP 8 DI 10.2337/dc13-2111 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275KV UT WOS:000328676000007 PM 24356591 ER PT J AU Aiello, LP AF Aiello, Lloyd Paul CA DCCT EDIC Res Grp TI Diabetic Retinopathy and Other Ocular Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study SO DIABETES CARE LA English DT Article ID INTENSIVE THERAPY; TRIAL; MELLITUS AB OBJECTIVETo evaluate whether intensive treatment (INT) with the goal of achieving blood glucose levels as close to the nondiabetic range as safely possible reduced the risk of onset and progression of diabetic retinopathy (DR) in subjects with type 1 diabetes (T1D) compared with conventional therapy (CON).RESEARCH DESIGN AND METHODSThe Diabetes Control and Complications Trial (DCCT) (1982-1993) was a multicenter, controlled clinical trial comparing INT with CON for onset and progression of DR. The Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994-present) is an observational follow-up of the DCCT cohort.RESULTSOf the 1,441 DCCT subjects, 726 had no DR (primary prevention cohort) and 715 had mild DR (secondary intervention cohort) at baseline. Subjects were followed for a mean of 6.5 years. INT median HbA(1c) was 7% compared with CON median of 9%. INT reduced the adjusted mean risk for the development of DR by 76% and slowed progression of DR by 54% compared with CON. Following DCCT, the HbA(1c) levels in the original INT and CON groups converged (year 8, INT 7.98%; CON 8.07%); nevertheless, the groups continued to have a durable effect of initial assigned therapy with significantly lower incidence of further DR progression in the INT group (hazard reduction 53-56%). Severe retinal outcomes and procedures to treat them were reduced by 50% in the original INT group.CONCLUSIONSINT delays the onset and slows the progression of DR. Furthermore, the early effects of metabolic control continue to accrue over many years despite subsequent comparable glycemic control (metabolic memory). These results emphasize the need for optimizing glycemic control as early as possible in patients with diabetes. C1 [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. EM lpaiello@joslin.harvard.edu FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK-094176, U01-DK-094157]; National Eye Institute; National Institute of Neurological Disorders and Stroke; Genetic Clinical Research Centers Program; Clinical and Translational Science Center Program, Bethesda, MD FX The DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1982-93, 2011-2016) and contracts (1982-2011) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (current grant numbers U01-DK-094176 and U01-DK-094157) and through support of the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the Genetic Clinical Research Centers Program (1993-2007), and Clinical and Translational Science Center Program (2006-present), Bethesda, MD. NR 15 TC 37 Z9 39 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2014 VL 37 IS 1 BP 17 EP 23 DI 10.2337/dc13-2251 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275KV UT WOS:000328676000014 PM 24356593 ER EF